Taiwanese Journal of Obstetrics and Gynecology

Projectile vomiting as presentation of duodenal intramural metastasis from cervical cancer

To report a case and review literature of bowel metastases from cervical squamous cell carcinoma. A 49-year-old woman with a history of FIGO 2013 stage IVB cervical squamous cell carcinoma presented with refractory nausea, projectile vomiting, anorexia, postprandial abdominal pain, and significant weight loss for six months. Restaging images didn't reveal viable tumors but thickened duodenal wall indicating gastric outlet obstruction. Initially, the etiology was masked by chronic erosive duodenitis and mistreated as a duodenal ulcer. After repeated gastrointestinal endoscopic biopsy confirming intramural duodenal metastasis from cervical squamous cell carcinoma, the patient was treated successfully by gastrojejunostomy and adjuvant chemotherapy. She has remained asymptomatic and disease-free for more than 12 months since the surgical metastasectomy. Intestine metastasis from cervical cancer is a rare cause that may present as projectile vomiting due to gastric outlet obstruction. Prompt recognition and surgical intervention may provide good outcomes despite the metastatic nature.

Genotype-specific prevalence of high-risk human papillomavirus among cytologically normal women in Taiwan

Taiwan launched human papillomavirus (HPV) DNA testing at ages 35, 45, and 65 years to improve cervical cancer screening. However, age- and genotype-specific prevalence data for high-risk HPV (hrHPV) in routine screening populations are limited. We aimed to provide the baseline genotype-specific hrHPV prevalence among cytologically normal women in New Taipei City. We conducted a cross-sectional study between 2022 and 2023 using opportunistic sampling within organized public sector screening services. Women aged ≥30 years underwent co-testing with a Papanicolaou (Pap) smear and HPV DNA using the Roche Cobas test. Descriptive statistics were used to report the hrHPV prevalence, including age distribution and screening history. Among 7,129 women with normal cytology, the overall high-risk HPV prevalence was 4.2 %. HPV-16-only and HPV-18-only accounted for 0.38 % and 0.22 %, with additional co-infections in 0.10 % and 0.03 %, respectively. The combined prevalence of the non-16/18 high-risk genotypes was 3.48 %. Both HPV-16 and HPV-18 were most frequently detected among women aged 45-54 years in terms of case distribution. Age-specific prevalence for overall hrHPV and HPV-16 peaked among women aged 30-44 years and declined significantly with increasing age (p-for-trend = 0.048 and 0.016, respectively). hrHPV prevalence did not differ significantly across Pap-smear screening intervals. Self-reported familiarity with HPV DNA testing was higher in women aged 30-35 years (44.6 %) and lowest in those ≥65 years (12.6 %). This study provided updated hrHPV prevalence estimates that may inform age-based screening strategies and underscored the need for genotype surveillance and risk-based triage approaches.

Mirvetuximab soravtansine-Gynx (MIRV) for treating platinum-resistant recurrent ovarian cancer

Cervical cancer: Part I human papilloma virus vaccination in Taiwan

A significant decline in both incidence and prevalence of cervical cancers after widespread-introducing cervical screening strategy by Papanicolau test (Pap test) has been found in the world, but cervical cancer is still one of the most common female cancers, reporting the fourth prevalence and also one of the leading causes to result in main women-associated morbidity and mortality, particularly for those women living in low- and middle-income countries. Cervical cancer is one of the most important health concerns directly destroying the global health-care system, partly because of not only increasing the disability either secondary to diseases themselves of victims or mediated by treatment-related adverse events to the survivors but also acting as a leading cause of death of diseased patients worldwide, alarming the urgent need to do something to minimize the catastrophic diseases-related heavy socioeconomic burden. It is fortunate that cervical cancer is a preventable disease, based on its strong association with human papillomavirus (HPV) infection (more than 95%), particularly for those high-risk HPV (HR-HPV) and its high possibility by detecting HPV infection before the development of cervical cancer as well as an effective prevention by HPV vaccination. That is why WHO (World Health Organization) considers cervical cancer as a public problem and attempts to accelerate the elimination of cervical cancer program by three-pillar approach (90:70:90% targets), including (1) 90% of girls are fully vaccinated with HPV vaccine by 15 years of age; (2) 70% of women are screened with a high-performance test by 35 and 45 years of age and precancerous lesions are treated early; and (3) 90% of women identified with cervical diseases receive appropriate and adequate treatment. Herein, this review focuses on the HPV vaccination as Part I, including global recommendations and Taiwan government's policy for HPV vaccination.

Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions

Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization. We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment. Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031). The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions.

Progesterone receptor isoform B in the stroma of squamous cervical carcinoma: An independent favorable prognostic marker correlating with hematogenous metastasis

To ascertain the prognostic role of the expression levels of estrogen receptor (ER) and progesterone receptor (PR) within the stroma microenvironment of cervical cancer and explore their correlation with clinical parameters. This retrospective cohort study involved patients with cervical cancer diagnosed and treated at Hualien Tzu Chi Hospital between 2000 and 2010. ERα, PRB, and PR (A + B) expression levels in 169 cervical carcinoma samples, including both the tumor and stromal components, were independently scored by two pathologists, and survival and clinicopathological parameters were analyzed. ERα or PRs were predominantly expressed in the stromal compartment rather than within cervical cancer cells. Their expression was observed comprehensively within the intra- and peritumor stroma cells. A stromal PRB expression significantly correlated with a lower 5-year mortality because of cervical cancer (p = 0.011). Particularly, levels of both stromal ERα and PRB expressions correlated with lower hematogenous distant metastase rates (p = 0.013 and p = 0.011, respectively). In the multivariable logistic regression analyses, stromal PRB independently conferred a lower risk of 5-year mortality (p = 0.022), regardless of age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation, lymphovascular space invasion, and lymphatic and hematogenous metastases. Moreover, the incorporation of stromal PR (A + B) and PRB expression in the FIGO stage significantly enhanced the accuracy of survival prediction. Stromal PRB expression emerges as an independent and favorable prognostic marker for cervical squamous cell carcinoma and correlated with a low risk of hematogenous metastases. The findings imply that incorporating this marker into the FIGO stage better predicts the survival for cervical cancer.

Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues

The therapeutic effect of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with epithelial ovarian cancer (EOC) with somatic BRCA mutations is consistent with that observed in patients with germline BRCA mutations, indicating the importance of detecting both germline and somatic BRCA mutations concurrently. We compared the efficacy of multi-gene panel next generation sequencing (NGS) in EOC patients' formalin-fixed, paraffin-embedded (FFPE) tissue to that of conventional Sanger sequencing in blood samples. This study included 48 patients with EOC, and both blood Sanger sequencing and FFPE tissue NGS were conducted in all of them. Clinical and pathological data were reviewed, including age at diagnosis, histology, and stage. Blood Sanger sequencing was performed using peripheral blood leukocytes. The target regions of 90 cancer-related genes were identified using FFPE tissue. The median age of patients was 56.1 years, with serous carcinoma (n = 40, 83.3%) and stage III (n = 37, 77.1%) being the most common histology and International Federation of Gynecology and Obstetrics (FIGO) stage, respectively. FFPE tissue NGS identified ten pathogenic variants, including all eight pathogenic variants identified by blood Sanger sequencing and two additional pathogenic variants. Furthermore, FFPE tissue NGS identified 19 variants of uncertain significance (VUS), including all ten VUS identified by blood Sanger sequencing and nine additional VUS. The FFPE tissue multi-gene panel NGS had 100% sensitivity for detecting BRCA germline mutations and could detect additional somatic mutations. Furthermore, performing FFPE tissue multi-gene panel NGS followed by blood Sanger sequencing sequentially may help differentiate germline from somatic BRCA mutations for genetic counseling.

Lower limb lymphedema after surgical staging for endometrial cancer: Current insights and future directions

Lower extremity lymphedema (LEL) is a common complication following surgical staging of endometrial cancer. LEL is a chronic condition associated with significant impact on patient morbidity and quality of life (QoL). This review aimed to report the current evidence in the literature on secondary LEL after surgical staging for endometrial cancer, focusing on the incidence based on different approaches to lymph node staging, diagnosis, risk factors, and the impact on QoL. Due to the absence of a standardized agreement regarding the methodology for evaluating LEL, the documented frequency of occurrence fluctuates across different studies, ranging from 0% to 50%. Systematic pelvic lymphadenectomy appears to be the primary determinant associated with the emergence of LEL, whereas the implementation of sentinel lymph node biopsy has notably diminished the occurrence of this lymphatic complication after endometrial cancer staging. LEL is strongly associated with decreased QoL, lower limb function, and negative body image, and has a detrimental impact on cancer-related distress reported by survivors. Standardization of lymphedema assessment is needed, along with cross-cultural adaptation of subjective outcome measures for self-reported LEL. The advent of sentinel lymph node mapping represents the ideal approach for accurate nodal assessment with less short- and long-term morbidity. Further research is needed to definitively assess the prevalence and risk factors of LEL and to identify strategies to improve limb function and QoL in cancer survivors with this chronic condition.

Clinicopathologic significance of mismatch repair protein expression in endometrioid endometrial cancer

To evaluate the association between mismatch repair (MMR) protein expression and clinico-pathologic outcomes in patients with endometrioid endometrial cancer (EC). A retrospective review of the clinico-pathologic outcomes was performed on patients who were diagnosed with EC and had results of MMR protein immunohistochemistry. MMR-deficient (MMR-d) was defined as absence of expression in any of the 4 MMR proteins (MLH1, MSH2, MSH6, and PMS2). Demographics, pathologic variables, and survival outcomes were compared according to the MMR status. A total of 193 EC patients with available MMR expression data were included, of whom 163 patients had endometrioid type EC. Overall, 44 patients (27.0%) were classified as MMR-d. Compared with MMR-proficient (MMR-p) group, MMR-d group was associated with more frequent lymphovascular space invasion (LVSI, p = 0.001). MMR-d was also related with higher risk of lymph node (LN) metastasis in endometrioid type EC (p = 0.008), especially para-aortic LN metastasis. During the median follow-up period of 19.1 months (1-44.5), MMR-d group, especially MLH1/PMS2 subgroup, showed a tendency of reduced PFS (p = 0.036 and p = 0.008, respectively). On Cox regression analysis, however, LN metastasis remained as the only independent risk factor for PFS (p = 0.004) in endometrioid EC, and MLH1/PMS2 loss showed a marginally significant association (p = 0.054). Our findings of the associations between MMR deficiency and poor prognostic factors, such as LVSI and LN metastasis, may suggest the prognostic value of MMR status in EC and need further prospective validation studies.

Duodenal stenosis due to small lymphocele after para-aortic lymphadenectomy: A case report and review of the literature

We present an unusual case of a small para-aortic lymphocele causing duodenal stenosis after lymphadenectomy and discuss its treatment. Our case involved a 57-year-old woman with endometrial cancer who underwent surgery, including para-aortic lymphadenectomy. On postoperative day 7, projectile vomiting occurred. Computed tomography (CT) revealed a small lymphocele in the dorsal duodenum, causing duodenal stenosis. Transpercutaneous and transduodenal puncture or surgical procedures were difficult because the cyst was too small. Per endoscopic and gastrointestinal series findings on the postoperative day 22, a liquid diet was presumed to be able to pass through the narrow portion. Hence, concentrated liquid food was administered orally; no vomiting occurred. At 2 months postoperatively, CT showed no lymphocele. Conservative treatment involving waiting for spontaneous lymphocele reduction with a concentrated fluid diet may be considered in such cases if fluid passage is confirmed with endoscopy and gastrointestinal series.

Treatment for recurrent epithelial ovarian cancer

CYLD expression in endometrial carcinoma and correlation with clinicohistopathological parameters

Endometrial cancer is a threat to women health worldwide. Cylindromatosis (CYLD) enzyme is a tumour suppressor, considered an effective prognostic marker in various malignancies, but its role in endometrial carcinoma is not fully elucidated. Here, we sought to estimate the prognostic value of CYLD expression in endometrial carcinoma. CYLD levels were immunohistochemically evaluated in 65 patients with endometrial carcinoma and inferential statistics were applied. Low or negative CYLD expression significantly correlates with older ages, non-endometrioid and invasive carcinomas, tumours with moderate or poor differentiation and advanced stages. Moreover, non-endometrioid and invasive carcinomas are independent risk factors for weaker CYLD expression. Kaplan-Meier analysis illustrated that negative or low CYLD expression is statistically significantly associated with increased death risk, compared to moderate or high expression. This study demonstrates for the first time a clear correlation between CYLD expression and clinicohistopathological parameters of endometrial carcinoma patients, suggesting its use as a potential prognostic/predictive marker for Endometrial Carcinoma.

Dose-dense chemotherapy with weekly paclitaxel and 3-weekly carboplatin for recurrent ovarian cancer

To analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review. Patients accepted weekly paclitaxel 80 mg/m Sixteen patients with recurrent ovarian cancer, including 1 platinum-resistant, 7 partially platinum-sensitive, and 8 platinum-sensitive, accepted a median of 6 cycles of chemotherapy (range 3-10). The overall response rate (ORR) and complete response (CR) rate were 93.8%, and 62.5%, respectively. The median PFS of all patients were 10.9 months (range 4.3-40.5). The median time to response (TTR) was 29.0 days (range 19.6-38.4). The median disease-free survival (DFS) after CR was 5.6 months (range 1.2-34.2). Grade 3 at least toxicity included anemia (6.3%), neutropenia (50%), and thrombocytopenia (18.8%). Twenty-nine articles on phase I, II, III, or retrospective studies of dose-dense chemotherapy with weekly paclitaxel were reviewed. This is the first report using Japanese Gynecologic Oncology Group 3016 protocol, weekly paclitaxel and 3-weely carboplatin, on recurrent ovarian cancer. The current study showed high ORR and CR with tolerable toxicities. Our study suggested dose-dense chemotherapy with paclitaxel, especially combining carboplatin created high efficacy probably by anti-angiogenesis. However, consolidation or maintenance therapy is needed to prolong DFS.

Chemoresistance in ovarian cancer (I)

Clinical impact of glandular involvement in high-grade squamous intraepithelial lesions of the cervix

The prognostic significance of glandular involvement in high-grade squamous intraepithelial lesions (HSIL) following cervical conization remains unclear. This research aimed to evaluate the clinical impact of glandular involvement on surgical outcomes. Between December 2019 and December 2020, 119 patients who underwent cervical conization were retrospectively observed. Patient characteristics, such as human papillomavirus (HPV) status, cytology results, glandular involvement, conization specimen depth and volume, margin status, and recurrence were collected and analyzed. Glandular involvement was significantly associated with positive endocervical margins (22.0 % vs. 6.5 %, p = 0.017), higher prevalence of preceding HSIL or CIN (cervical intraepithelial neoplasm)2/CIN3 cytology (60.4 % vs. 42.0 %), and increased HPV16 infection among high-risk HPV positive patients (69.2 % vs. 34.8 %, p = 0.050). No significant differences were observed in recurrence rates among patients with HSIL with or without glandular involvement. Multivariable analysis identified that margin status is the only independent predictor of recurrence (positive margin: OR [odds ratio] 26.85, 95 % CI [confidence interval] 2.59-277.86, p = 0.006 or uncertain margins: OR 29.90, 95 % CI 1.09-818.17, p = 0.044). While glandular involvement in HSIL is associated with positive endocervical margins, abnormal preceding cytology, and higher risk of HPV16 infection, it does not independently predict recurrence following conization. Instead, positive surgical margins are the primary factor of recurrence, highlighting the value of achieving complete excision to optimize patient outcomes.

Complete remission of advanced and recurrent cervical cancer with pembrolizumab treatment- 3 case reports

Recurrent cervical cancer is hard to treat when occurring in a previous radiated area and unresectable or distant metastasis. We present three such cases who achieved complete remission (CR) after chemoradiotherapy and pembrolizumab. Case 1 was diagnosed with cervical adenocarcinoma, stage IVB. She obtained CR after concurrent chemoradiotherapy (CCRT) and post-CCRT adjuvant chemotherapy and bevacizumab. Recurrence at previous irradiated sacral bone was controlled with pembrolizumab and CCRT using proton therapy (PT). Case 2 was diagnosed with stage IVB squamous cell carcinoma. First recurrence occurred at inguinal lymph node (LN). Secondary recurrence occurred at paraaortic LN ten years later. PT with chemotherapy and pembrolizumab achieved CR. Case 3 had a small cell carcinoma (stage IVB) with bone metastasis. She had CR to CCRT with etoposide-cisplatin. Liver metastasis was salvaged with CCRT and pembrolizumab. CCRT with pembrolizumab is potentially curative for recurrent cervical cancer conventionally amenable for palliation.

The oncological and obstetric outcomes of cervical squamous cell carcinoma at stage IA1 managed with the loop electrosurgical excision procedure

To evaluate the efficacy and superiority of loop electrosurgical excision procedure (LEEP) in managing stage IA1 cervical microinvasive squamous cell carcinoma (MISCC) without lymph-vascular space invasion (LVSI). The oncological and reproductive outcomes of a series of patients affected by stage IA1 MISCC without LVSI, initially treated by LEEP between February 2006 and December 2017, were retrospectively reviewed. Ultimately, 109 patients were included. The mean age at diagnosis was 35.4 years old, and 36 patients were nulliparous. Multifocal lesions were identified in 15 patients (13.8%). The mean cone depth was 17.4 mm. Resection margins were positive/unevaluable and negative in 26 (23.9%) and 83 (76.1%) cases, respectively. Among cases undergoing salvage treatments, the residual disease rate for patients with positive/unevaluable margins was significantly higher than those with negative margins (P = 0.003). During the follow-up period of 43.0 ± 28.9 months, no relapse was identified. Fifteen of 20 patients (75.0%) conceived successfully, with a full-term live birth rate of 93.3%. For stage IA1 MISCC without LVSI unexpectedly found in a loop excision, initial LEEP with clear margin is efficient and adequate. For cases with multifocal MISCC, or for those young patients who wish to become pregnant in the future, LEEP is the optimal choice.

KELIM score and BRCA status are unreliable to predict the completeness of cytoreduction during interval debulking surgery with hyperthermic intraperitoneal chemotherapy for ovarian cancers

The gold standard for treating primary advanced ovarian, primary peritoneal, and fallopian tubal cancers (OC) is optimal debulking surgery plus adjuvant chemotherapy. Neoadjuvant chemotherapy followed by optimal interval debulking surgery (NACT/IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) provides better survival outcomes than without HIPEC in current literature. The modeled CA-125 elimination rate constant k (KLEM) score reflects the response of NACT before IDS. A BRCA mutation may indicate a better response to chemotherapy and improved outcomes in OC. However, the correlation between these two factors and the completeness of cytoreduction (CC) during IDS/HIPEC has been less extensively discussed. We retrospectively enrolled 17 HIPEC cases, including 10 NACT/IDS and seven secondary cytoreductive surgery (SCS) cases after database searching and chart review. The KELIM score was calculated in the NACT/IDS group for predicting the residual status of surgery. The survivorship between NACT/IDS and SCS was similar. There is no major surgical complication, morbidity or mortality after HIPEC. In the IDS group, five cases reached CC scores of 0 (however, two of these cases had an unfavorable KELIM score), four cases reached a CC of 1, and one case had a CC of 2, but with a favorable KELIM score. In the SCS group, three cases reached a CC of 0, two reached a CC of 1, and two reached a CC of 2. There was no serious post-operative morbidity or mortality after HIPEC. The KELIM score showed a weak correlation with the CC score. Two cases with BRCA 1/2 mutation showed unfavorable KELIM scores and only one case reached CC of 0. After the maturation of the HIPEC techniques, this procedure is safe and feasible. Currently, there are no reliable pre-operative markers, including KELIM score or BRCA1/2 status, which could predict the CC score after surgery.

Advanced high-grade serous carcinoma of the ovary after IVF treatment in a 38-year-old nulligravida: A case report of diagnostic challenges in the presence of OHSS

When there is massive ascites in a patient who has recently undergone IVF treatment, differentiating OHSS from ovarian cancer can be challenging. A detailed evaluation combining clinical history, ultrasound characteristics, and laboratory findings is essential. In cases where these initial evaluations are inconclusive, advanced imaging and histopathological examination may be necessary to achieve an accurate diagnosis. We report the case of a 38-year-old nulligravida woman with no family history of breast or ovarian cancer who presented with progressive exertional dyspnea and massive ascites six weeks after completing two cycles of in vitro fertilization (IVF) at a private fertility clinic. She was initially diagnosed and treated for ovarian hyperstimulation syndrome (OHSS)at the clinic, a known complication of controlled ovarian stimulation at the clinic. However, her symptoms persisted and progressed beyond the typical 10-14-day resolution period for mild-to-moderate OHSS. Upon presentation to our internal thoracic outpatient department, physical examination and imaging revealed right-sided pleural effusion and estimated ascites more than 2000 mL. Abdominal computed tomography demonstrated a large, multilocular, hypodense cystic mass measuring 12 × 12 cm originating from the right adnexa, accompanied by bilateral pleural effusions and diffuse ascites, raising suspicion for an underlying ovarian malignancy. The patient underwent thoracentesis and paracentesis twice within a seven-day interval, each time draining over 200 mL of pleural fluid and 2500 mL of ascitic fluid. Despite repeatedly negative cytological findings, the clinical course and radiologic features warranted surgical exploration. Laparotomy confirmed the diagnosis of high-grade serous carcinoma of the ovary with extensive peritoneal and pleural metastases. Given the patient's strong desire for fertility preservation, a suboptimal debulking procedure was performed, including right salpingo-oophorectomy, left salpingectomy, left ovarian cystectomy, tumor debulking, omentectomy, and enterolysis. Postoperatively, she commenced chemotherapy with carboplatin and paclitaxel. Although BRCA1/2 testing was negative, she was found to carry a homologous recombination repair (HRR) mutation, and maintenance therapy with a PARP inhibitor is being considered. Additionally, adoptive immunotherapy with cytokine-induced killer (CIK) cells is under evaluation as part of a multimodal treatment approach. This case highlights the diagnostic challenges in differentiating OHSS from malignancy in IVF patients with persistent and atypical symptoms. Comprehensive diagnostic approaches, including imaging and surgical exploration, are crucial for accurate diagnosis and appropriate management.

HER2 mutation profiling in mucinous ovarian carcinoma: Inferences for Enhertu (trastuzumab deruxtecan) as a potential therapeutic approach

This study aimed to characterize HER2 mutations in Taiwanese mucinous ovarian carcinoma (mOC) and evaluate the potential of Enhertu (T-DXd) as a targeted therapy for HER2-mutant mOC. We previously reported a 33.3 % (n = 7/21) HER2 tyrosine kinase domain (TKD) missense mutation rate in mOC using hot-spot PCR and Sanger sequencing. In this study, HER2 mutations were assessed in 18 additional mOC samples using targeted next-generation sequencing (NGS). Data from earlier PCR (n = 21) and current NGS (n = 18) were combined, resulting in all 39 cases. The COSMIC database and PolyPhen-2 (Polymorphism Phenotyping v2) algorithm were used to evaluate the pathogenicity of HER2 mutations identified in the NGS cohort. HER2 mutations were detected in 43.6 % (n = 17/39) of cases. The PCR cohort (n = 21) from the previous 2 studies using PCR and Sanger sequencing identified seven TKD mutations. On the other hand, the NGS cohort (n = 18) from the present study using targeted NGS detected ten non-TKD mutations, with p.P1170A being the most frequent. PolyPhen-2 pathogenicity predictions indicated that p.P1170A and p.R143Q were likely pathogenic. Combining PCR and NGS data enhanced statistical power; however, the study was limited by the insufficient residual specimens from the PCR cohort for NGS reanalysis. Our findings reveal a high prevalence of HER2 mutations in mOC, with distinct profiles in TKD and non-TKD regions. These results support further investigation of Enhertu (T-DXd) as a promising targeted therapy for HER2-mutant mOC. Larger, multi-center studies are needed to validate these findings and explore clinical applications.

Post-operative umbilical cellulitis probably related to incidental colonic puncture by Veress needle entry during insufflation

Laparoscopic surgery has become increasingly prevalent in modern gynecologic practice. However, this approach is not without risks. The most dangerous step is insufflation of the abdomen using a Veress needle or the blind creation of the camera port at the beginning of the surgery. Here, we report an interesting case of an umbilical camera port abscess, probably resulting from an incidental puncture of the colon by a Veress needle during initial insufflation. A 61-year-old Taiwanese postmenopausal woman underwent laparoscopic surgery for bilateral adnexal solid masses, incidentally discovered during regular follow-up for B-cell lymphoma. Insufflation and trocar placement were uneventful, but over-distended colon was observed without an identifiable cause. Bilateral broad ligament myomas, enlarged right ovarian solid mass, and an atrophic left ovary were noted. Only a right salpingo-oophorectomy was performed, and final pathology revealed a benign Brenner's tumor. Postoperative fever and leukocytosis occurred but subsided spontaneously. However, the patient later experienced spiking fever and a significant abscess at the umbilical trocar site. The abscess culture confirmed the presence of enteric bacteria. Her condition improved with broad-spectrum antibiotic therapy and wound care. An incidental puncture of colon by a Veress needle can lead to over-distension of the colon and bacterial contamination of the umbilical port tract. Greater postoperative vigilance and timely antibiotic coverage may help prevent this rare complication.

High frequency of BRAF mutations and concomitant KRAS mutations in Taiwanese ovarian clear cell carcinoma

Given encouraging clinical evidence of BRAF inhibitors for melanoma, etc., we investigated BRAF mutation status in ovarian clear cell carcinoma (OCCC) from Taiwanese women and assessed the association of BRAF mutation with KRAS mutation. DNA was extracted from microdissected tissue samples and analyzed for BRAF mutations in exon 15, around the activation segment (AS), using a highly sensitive BRAF mutant enrichment kit (FemtoPath®) with Sanger sequencing. All 17 OCCC cases were evaluated. 16 (94.12 %) harbored BRAF missense mutations, categorized as Class I - p.V600M (n = 3); Class II - p.A598V (n = 8), p.T599I (n = 10); Class III - none; and unclassified (UC) variants - p.A598T (n = 1), p.A598I (n = 1), p.S602A (n = 1), p.S602F (n = 7). These mutations occurred as single-point (n = 6), double-point (n = 5), or triple-point (n = 5) mutations. The most frequent mutation observed was p.T599I (n = 10), followed by p.A598V (n = 8) and p.S602F (n = 7). The p.A598I, p.S602A, and p.S602F are novel BRAF alterations. Merging our previous KRAS data, we found that concurrent KRAS and BRAF mutations in 11 of 17 cases (64.71 %) suggest a possible synergistic effect in OCCC tumorigenesis. Activating BRAF mutations are common in OCCC in Ascian Taiwanese, with p.T599I most prevalent. This suggests the potential for reduced response to current BRAF V600 inhibitors but possible sensitivity to dual BRAF/MEK or MEK inhibitors, other multi-targeted approaches, and new avenues for cancer immunotherapy. Further studies are encouraged to investigate the clinical benefits of these approaches for advanced OCCC with various BRAF mutation classes.

Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer: Current evidence and clinical perspectives

Recurrent epithelial ovarian cancer (rOC) remains a major therapeutic challenge because of its high relapse rate and the progressive development of chemoresistance. Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been explored as locoregional strategies to overcome the limitations of systemic therapy, but their clinical value varies substantially according to platinum sensitivity, surgical completeness, and patient selection. In platinum-sensitive rOC (PS-rOC), evidence from randomized controlled trials (RCTs) demonstrates that S-CRS provides survival benefit only when completeness of CRS (C-CRS) to CCR0 is achieved in rigorously selected patients using validated selection tools. Meta-analytic data further confirmed that incomplete resection confers little clinical advantage and may fail to offset surgical morbidity. The addition of HIPEC to S-CRS in this setting is supported by a biologically plausible rationale and has been associated with an overall survival (OS) benefit, although no consistent improvement in progression-free survival (PFS) has been demonstrated and treatment-related adverse events (TRAEs), particularly hematologic and renal AEs, are increased. These findings support a selective, center-experienced, and protocol-conscious application of HIPEC rather than routine use. In contrast, high-level evidence supporting S-CRS or S-CRS plus HIPEC in platinum-resistant rOC (PR-rOC) remains lacking. Available data are derived primarily from small retrospective series and systematic reviews with substantial heterogeneity and selection bias, precluding definitive conclusions regarding survival benefit. Several ongoing phase III RCTs are expected to clarify the optimal role, timing, and patient selection for HIPEC-based strategies across different disease settings. Overall, current evidence supports an individualized, biology-driven approach to rOC, integrating surgical feasibility, anticipated systemic treatment efficacy, and careful risk-benefit assessment within a multidisciplinary framework.

Immunology and therapeutic strategies in ovarian cancer

Epithelial ovarian cancer (OC) remains a lethal gynecologic malignancy, with approximately 70 % of patients relapsing within three years of frontline treatment. A clinically useful framework is to view advanced-stage ovarian cancer (ads-OC) as "two diseases" rather than a single uniform entity: one reflecting the classic course guided by the platinum-free interval (PF-I), and the second highlighting biologically defined subgroups where repeated relapses occur across multiple lines. This framework implies that optimal management should not be determined by PF-I alone but should be individualized using integrated disease biology and treatment context. Within these pathways, immunotherapy (IOT) has transitioned from ineffective monotherapy toward rational combination strategies designed to modulate the tumor microenvironment (TME) and overcome dominant immunosuppressive forces, such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs). Recent clinical evidence from the phase III ENGOT-ov65/KEYNOTE-B96 trial represents a historic milestone, demonstrating that the addition of pembrolizumab to weekly paclitaxel, with or without investigator-choice bevacizumab, significantly improves overall survival (OS) in patients with platinum-resistant rOC (PR-rOC) with PD-L1-expressing tumors, with OS benefit also observed in the intention-to-treat (ITT) population. These findings validate the potential of immune checkpoint inhibitor (ICI)-based regimens to reshape the therapeutic landscape in populations with substantial unmet need. Furthermore, biomarker development is moving toward a more structured framework, as proposed by SITC and NCI, emphasizing the need for standardized reporting and the exploration of emergent indicators. Institutional research further highlights that IOT-relevant biomarkers, such as PD-L1, are not fixed baseline characteristics but are dynamically upregulated by cytotoxic stress and cisplatin exposure, reflecting a compensatory immune-evasive state linked to platinum resistance. Ultimately, the management of rOC is evolving into a biologically informed, line-specific strategy that prioritizes the integration of IOT within established systemic backbones. The success of contemporary combination approaches underscores the necessity of interpreting biomarkers within a dynamic, treatment-contextualized framework. Future progress will depend on a bidirectional lab-to-trial paradigm, where mechanistic insights into treatment-induced immune modulation guide the design of precise clinical trials, ensuring that therapeutic strategies are tailored to the evolving immune context of each patient throughout the disease continuum. Beyond ICI, immune-relevant strategies targeting treatment-induced resistance pathways, exemplified by glucocorticoid receptor (GR) antagonism in the ROSELLA trial, suggest that indirect TME modulation may also yield clinically meaningful benefit in PR-rOC.

Laparoscopic-assisted vaginal hysterectomy versus total laparoscopic hysterectomy in endometrial cancer: A retrospective cohort study

The methods of laparoscopic staging surgery (LSS) for endometrial cancer can generally be classified into two approaches: laparoscopic-assisted vaginal hysterectomy (LAVH)-based LSS and total laparoscopic hysterectomy (TLH)-based LSS. This study aims to compare perioperative and oncologic outcomes between LAVH-based LSS and TLH-based LSS. Between January 2019 to December 2024, 118 patients who underwent laparoscopic staging surgery were retrospectively observed. Patient characteristics, such as age, BMI, parity, disease extension, histology subtypes, estimated blood loss, operative time, complications and recurrence were collected and analyzed. TLH was associated with significantly lower estimated blood loss compared with LAVH (119.0 ± 69.9 vs. 218.5 ± 375.1 mL, p = 0.036). TLH also offered a tendency of shorter operative time but without significance (197.40 ± 50.74 vs. 214.41 ± 66.89 min, p = 0.135). While hospital stay, complication rate, and 30-day re-hospitalization were comparable between groups. Four recurrences were observed, all in the LAVH group. Kaplan-Meier analysis showed no significant difference in progression-free survival (p = 0.300). TLH-based LSS in early-stage EC appears a safe approach, offering reduced blood loss without compromising perioperative or oncologic outcomes compared with LAVH-based LSS.

Brain metastasis from ovarian carcinoma: Analysis of eight cases from a single radiotherapy center

Brain metastasis from epithelial ovarian carcinoma (EOC) is rarely seen having rate of 1-3% with very poor prognosis. Studies on brain metastatic EOC is limited with low number of participants. An increasing trend in EOC related to brain metastasis has been reported recently confronting managing clinicians with new challenges. Therefore, more information on this issue is needed. We aimed to analyze a single radiotherapy center experience on EOC related brain metastases. Data of all patients treated between January 1998 and December 2016 at a radiation center of a university hospital were reviewed retrospectively. Clinicopathological characteristics, treatment details and outcome were analyzed. We identified only ten cases with EOC related brain metastasis in our department during 18-year period. Two patients were excluded because of data unavailability and therefore our study was performed among 8 patients. The median time between EOC diagnosis and detection of brain metastasis was 19.8 months. Brain metastasis was multiple in majority (75%). Extracranial metastasis at the time of brain metastasis was 62.5%. All patients died in the follow-up. The median survival time after the diagnosis of brain metastasis was 4.5 months. The median overall survival (OS) after the diagnosis of EOC was 28.9 months. The interval between the initial diagnosis and brain metastasis was negatively correlated with survival after brain metastasis (B-OS) occurred as time interval (p = 0.047). Presence of extracranial metastasis at time of occurrence of brain metastasis and application of multimodal treatment after brain metastasis were positively correlated with B-OS time (p = 0.007, p = 0.046, respectively). Prognosis of brain metastasis from EOC remains poor. The factors associated with better B-OS were the longer time between initial diagnosis and brain metastasis, absence of extracranial disease at time of brain metastasis, and application of the multimodal treatment.

Transcervical resection of myoma (TCRM): Part I

Uterine fibroids occur frequently in women during the reproductive age, and they are rarely associated with clinical meaning because of their benign characteristics and asymptomatic clinical presentation. Sometimes, uterine fibroids are symptomatic and associated with compression syndrome, infertility, chronic pelvic pain and heavy menstrual bleeding. All need further intervention and treatment. Medication is often preferred and frequently applied but symptom-control rate is varied, resulting the need of further active treatment. An effective but minimally invasive procedure such as surgery is sometimes used as back up strategy in the management of women with no response to medical treatment. Additionally, fertility-sparing or uterus-preservation is the main goal and becomes very popular in both physicians and patients. Conservative surgical treatment can be made according to myoma location. Simply, myoma is classified as submucosal, intramural and subserous types. However, to offer a practical standardized consensus for the description and categorization of myomas, the International Federation of Gynaecology & Obstetrics (FIGO) classification system from type 0 to type 8 is established, which is often used for guiding patient management and offering prognostic information, because submucosal myoma (FIGO type 0, 1, probable 2, and possible 3) is frequently associated with symptoms or signs, needing a further intervention. Transcervical resection of myoma (TCRM, also called as hysteroscopic myomectomy: HM) is the treatment of choice for submucosal myoma, and this increased trend is secondary to its nearly non-trauma in nature, even compared to other MIS, such as mini-laparotomy and laparoscopic or robotic approach. Although TCRM is becoming more and more popular in modern clinical practice, the risks and limitations of TCRM are often overlooked. In this review as part I, we will focus on the rationale, efficacy, complication, and limitation of using TCRM in the management of women with symptomatic uterine fibroids. Under the well-training and carefully performing TCRM, TCRM not only provides the less traumatic injury to the uterus, but also offers an effective and safe strategy in dealing with symptomatic submucosal myoma.

Primary melanoma of the vagina with urethral invasion: A case report and literature review

A rare case of gestational ovarian choriocarcinoma coexistent with intrauterine pregnancy

To report the rare case of gestational primary ovarian choriocarcinoma coexistent with intrauterine pregnancy, successfully treated with surgery and systemic chemotherapy. We also describe the utility of short tandem repeat (STR) genotyping in the diagnosis of choriocarcinoma. A 38-year-old woman at 17 gestational weeks presented with an ovarian tumor rupture in the left ovary. Left salpingo-oophorectomy was performed and the patient was diagnosed with gestational ovarian choriocarcinoma via histopathology and STR genotyping. After artificial abortion, the patient underwent 8 cycles of chemotherapy. Abdominal hysterectomy was performed because of the presence of low levels of human chorionic gonadotropin and the tumor that developed behind the uterus. However, no viable choriocarcinoma cells were found in the residual tumor, suggesting that the patient achieved full remission. Early detection is crucial in treating choriocarcinomas; thus, clinicians should consider the possibility of choriocarcinoma at the presence of an ovarian tumor during pregnancy. Gestational and non-gestational choriocarcinomas differ in prognosis and sensitivity to chemotherapy due to their different etiologies. Therefore, STR genotyping may be beneficial in predicting the patient's prognosis or selecting the appropriate regimen.

Appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital, in Southern Thailand

To evaluate the prevalence of appendiceal tumors in patients diagnosed with mucinous ovarian tumors and to determine factors associated with coexisting appendiceal tumors. Retrospective review of all patients who were diagnosed with mucinous ovarian tumors and underwent an appendectomy during surgery between January 2002 and June 2017 was performed. Univariate and multivariate logistic regression analyses were used to identify risk factors for coexisting appendiceal tumors. A total of 303 patients with mucinous ovarian tumors who underwent appendectomy were identified, including 77 (25.4%) mucinous cystadenoma and 226 (74.6%) mucinous borderline tumor or carcinoma. Twenty-one (6.9%) had coexisting appendiceal tumors including 8 that were primary appendiceal mucinous adenocarcinomas, 6 low-grade appendiceal mucinous neoplasms, 6 secondary appendiceal metastasis from the ovary, and one hyperplastic polyp. None of mucinous cystadenoma had coexisting appendiceal tumors. Multivariate analysis revealed advanced age ≥50 years, previous rupture of ovarian tumors, abdominal extension of tumors, and grossly abnormal appendix were independent factors for coexisting appendiceal tumors. Prevalence of coexisting appendiceal tumors in mucinous ovarian tumors was not uncommon. The risk factors were grossly abnormal appendix, abdominal extension of tumor, previous rupture of ovarian tumors, and advanced age.

Absence of PIK3CA mutation in primary mucinous ovarian carcinoma: An analysis of 20 Taiwanese cases by FemtoPath PIK3CA mutation screen kit

Non-Hodgkin's B-cell lymphoma of the ovary: A case report and review of the literature

To report a case and review published cases of non-Hodgkin's lymphoma of the ovary. A 30-year-old female presented with abdominal fullness. Abdominal CT revealed bilateral huge ovarian masses with moderate amount of ascites. Explore laparotomy was performed and the frozen section of right ovarian mass reported to be malignant lymphoma. The final diagnosis was Ann Arbor stage IV diffuse large B cell lymphoma. The patient received six cycles of chemotherapy with RCHOP regimen. She achieved complete remission after the treatment, and there's no evidence of recurrence after 12 months follow up. Ovarian lymphoma is a rare condition. It could present with findings mimicking ovarian cancer. Chemotherapy is the main treatment option and cytoreductive surgery should be avoided.

Correlation between HPV-negative cervical lesions and cervical microenvironment

To investigate the correlation between high-risk human papillomavirus (HR HPV)-negative cervical lesions and cervical microenvironment in Inner Mongolia, China, and to find the pathogenic factors of HR HPV-negative cervical lesions. 74 cases of HR HPV-negative healthy women and 80 cases of patients with cervical lesions (28 cases of LSIL, 49 cases of HSIL and 3 cases of CSCC) were selected as the study group; 26 cases of HPV-positive women and 352 cases of patients with cervical lesions (108 cases of LSIL, 214 cases of HSIL and 30 cases of CSCC) were control group. Questionnaires were collected from the study group and the control group and specimens were collected. Gram staining, hematoxylin and eosin staining microscopy, and substrate colorimetry method were used to detect vaginal micro-ecological indicators; ELISA was used to detect the concentration of SIgA, IgG, IL-2 and IL-10 in vaginal lavage fluid. Genetic testing was used to detect HPV, mycoplasma, and chlamydia infection. The changes of vaginal micro-ecology evaluation index and local immune factor concentration in healthy women and cervical lesions of all grades in the study group and the control group were compared. Patients with cervical lesions, compared with healthy women, had a decrease in dominant lactobacilli and dysbacteriosis (P < 0.05), and this trend became more apparent as the disease progressed. The diversity and concentration of the flora in the HPV-negative group increased, the abnormal composition ratio decreased, and the HPV-positive group showed the opposite trend. As the lesion progressed, H This study showed that vaginal micro-ecological imbalance and weakening of local cervical immune function are important reasons for the development of cervical lesions. It is expected to inhibit the development of cervical lesions by regulating the balance of vaginal micro-ecology and enhancing local immune function. By detecting Lactobacillus vaginalis, pre-enzyme, IL-2, IL-10, SIgA, it can guide the further diversion of HPV-positive women and predict the development direction of cervical lesions after HPV infection.

Primary vaginal leiomyosarcoma: A case report with complete morphological, immunohistochemical and ultrastructural study

Primary vaginal leiomyosarcomas (LMS) are rare, easily recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management. A nodular, 25 × 23 x 28 mm-mass, infiltrating the urethra, was found in a 58-year-old woman. A biopsy showed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. An anterior pelvic exenteration was performed. The sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy, confirming the diagnosis of LMS. Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice and surgical resection is generally the gold standard in these cases.

Circulating tumor cells as a “real-time liquid biopsy”: Recent advances and the application in ovarian cancer

Even with the latest advances in technology, the treatment of ovarian cancer remains a big challenge because it is typically diagnosed at advanced stage, is prone to early relapse in spite of aggressive treatment and has an extremely poor prognosis. Circulating tumor cells (CTCs) can be used as a non-invasive "real-time liquid biopsy", which has shown the value of diagnosis, assessment of prognosis and chemoresistance, and detection of small residual tumors on ovarian cancer. This review article provides an overview on recent research on CTCs in ovarian cancer, with special focus on the clinical application of CTC tests.

Second primary malignancies after ovarian cancer: A SEER-based analysis (1975–2016)

To investigate the risk of occurrence of second primary malignancies (SPMs) in survivors of ovarian cancer (OC) using large data from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple primaries standardized incidence ratios (MP-SIRs) to calculate the risk of developing second primary malignancies after a diagnosis of ovarian cancer. Of our included 59,880 women with OC, 3972 cases (6.6%) developed 4495 s primary malignancies over an average follow-up period of 114.39 (±102.66) months. Overall, the risk of occurrence of second primary malignancies after a diagnosis of OC was greater than what would be expected for a reference US population (SIR = 1.05, 95%CI = 1.02-1.08, p-value < 0.05). The occurrence of second myeloid malignancies and second thyroid cancer were most notable across our latency periods. Among the most significant second primary malignancies by latency were malignancies of the appendix (SIR = 14.04, 95%CI = 5.65-28.93, p-value <0.05) at 2-11 months, the small intestine (SIR = 3.15, 95%CI = 1.76-5.2, p-value <0.05) at 12-59 months, and the urinary bladder (SIR = 1.63, 95%CI = 1.3-2.02, p-value <0.05) after 10 years of an OC diagnosis. Women with OC are at significant risk for the development of second primary malignancies across all sites, as compared to a reference US population, and may benefit from second primary malignancies site-specific screening post-diagnosis.

Early-stage granulosa cell tumor with pelvic recurrence and lung metastasis 16 years later: A case report and review of the literature

Only a few cases of early-stage ovarian granulosa cell tumor (GCT) with lung metastasis have been previously documented in the literature. We present a case of stage IA adult-type ovarian GCT with late pelvic recurrence and lung metastasis and review the relevant literature. A 71-year-old female who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for an ovarian GCT in her early 50s presented with pelvic recurrence 16 years later. Lung metastasis was accidentally discovered during a preoperative computed tomography scan of the pelvic tumor. The patient received surgical resection and adjuvant chemotherapy. She remains alive and healthy without evidence of disease after 12 months of follow up. This case illustrates the importance of long-term follow-up for early-stage GCTs. It also highlights the requirement of extended examination for possible extra-abdominal/pelvic tumors.

Coexisting cancers with atypical glandular abnormalities by liquid-based cytology: A retrospective study in tertiary hospital in a high cervical cancer incident country

To determine the incidence of coexisting cancers in women with glandular cell abnormalities detected from liquid-based cytology and to compare the detection rate of premalignant and malignant lesions among various subtypes of glandular cell abnormalities. From January 2014 to December 2016, liquid-based cytology was performed in 85,517 women. Using the Bethesda system 2001 criteria, abnormal cervical cytology was diagnosed in 3650 women (4.3%). Glandular cell abnormalities were diagnosed in 110 women (0.13%). Ten women with pre-existing genital tract cancers and 13 women who lost to follow up were excluded. Clinical characteristic, colposcopic finding, and histopathological data were reviewed in 87 women. High-grade premalignant and malignant lesions were diagnosed in 34 patients (39.1%). Co-existing cancer was diagnosed in 31 patients (35.6%); 15 cervical cancers (17.2%) and 16 endometrial cancers (18.4%). The detection rate of significant lesions (CIN2+ or malignant lesions) in patients with AGC-NOS was 14.9%, AGC-FN was 38.9% and AIS/adenocarcinoma was 90.9% (p < 0.001). Glandular cell abnormalities associated with high incidence of coexisting endometrial and cervical cancers. Comprehensive genital tract screening to evaluate gynecologic malignancy is strongly recommended in all women with glandular cell abnormalities.

Hinokitiol induces cell death and inhibits epidermal growth factor-induced cell migration and signaling pathways in human cervical adenocarcinoma

The aim of this study was to examine the antitumor activity of hinokitiol for its clinical application in the treatment of human cervical carcinoma. Cervical carcinoma HeLa cells were treated by different concentrations of hinokitiol. Flow cytometry was used to analyze cell cycle. Senescence-associated β-galactosidase (SA-β-gal) assay was used to identify senescent cells. The effects of hinokitiol on EGF-induced cell migration were determined by wound healing and transwell migration assays. Western blot was used to detect proteins involved in cell cycle progression, apoptosis, autophagy, and EGF-induced signaling pathways. Hinokitiol suppressed cell viability in a dose-dependent manner. Flow cytometric analysis indicated that hinokitiol treatment resulted in cell cycle arrest at G1 phase, with reduced number of cells in the G2/M phase. Western blot analysis further demonstrated that hinokitiol treatment increased the levels of p53 and p21, and concomitantly reduced the expression of cell cycle regulatory proteins, including cyclin D and cyclin E. SA-β-gal assay showed that hinokitiol treatment significantly induced β-galactosidase activity. In addition, treatment with hinokitiol increased the accumulation of the autophagy regulators, beclin 1 and microtubule-associated protein 1 light chain 3 (LC3-II), in a dose-dependent manner; however, it did not induce caspase-3 activation and poly ADP ribose polymerase (PARP) cleavage. In addition, epidermal growth factor-induced cell migration and c-Jun N-terminal kinase (JNK) and focal adhesion kinase (FAK) phosphorylation were significantly inhibited by hinokitiol. Our findings revealed that hinokitiol might serve as a potential therapeutic agent for cervical carcinoma therapy.

Laparoscopic versus open radical hysterectomy in women with early stage cervical cancer: A systematic review and meta-analysis

This review aimed to evaluate the short term and long-term outcomes of laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for early-stage cervical cancer. A search of PubMed, Medline and Scopus databased from 2000 to 2018 was conducted. Thirty studies were retrieved including 22 retrospective cohort studies and 8 prospective cohort studies. LRH was comparable with ARH in 5-year overall survival (RR = 1.0. 95%CI 0.98-1.03; p = 0.33) and 5-year disease-free survival (RR = 1.02 95%CI 0.97-1.06; p = 0.98). The majority of included studies reported the negative cancer factors which drive adjuvant therapy were similar between two approaches. LRH was associated with lower blood loss and blood transfusion, less postoperative complication, shorter hospital stays and similar intraoperative complication rate compared to ARH. Our data suggested LRH for early-stage cervical cancer was as safe and effective in terms of long-term outcomes, but with lower surgical morbidities.

Genistein inhibits migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways

Genistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes. HeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 μM, 12.5 μM, 25 μM, 50 μM and 100 μM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 μM genistein, the migration ability was detected by the scratch assay. Transwell assay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively. The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 μM. After treatment with 100 μM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 μM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist. Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.

Functional polymorphism of PIN1 rs2233679 is associated with the progression of CIN to early cervical cancer in Hunan Chinese

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) involves alteration of the structure, function, intracellular localization and/or stability of the phosphorylated protein on serine or threonine residues which relates to inflammation and tumorigenesis. Association between PIN1 promoter polymorphisms and cancer risk were reported in several cancers. We intend to study the relationship between the polymorphism of PIN1 promoter and cervical cancer initiation and development. We genotyped two common single nucleotide polymorphisms (SNPs) (rs2233678 and rs2233679) in the promoter of the PIN1 gene in healthy controls, patients with CIN or cervical cancer. We used polymerase chain reaction and DNA sequencing methods to analyze these two SNPs in 179 patients and 223 healthy controls. Luciferase activity assay was used to detect PIN1 expression driven by the rs2233679. The results revealed that the carriers of rs2233679 genotypes CT/TT had a significantly increased risk of cervical cancer in patients with CIN compared with genotype CC (odds ration [OR] = 2.924, 95% confidence interval [CI] = 1.093-7.819, P = 0.033). Luciferase activity assay results revealed that PIN1 expression driven by the rs2233679 genotype TT was higher than the genotype CC (P < 0.05). On the other hand, no significant correlation between the healthy controls and patients was found for PIN1 rs2233678 which showed that rs2233678 genotypes CG/GG is 95% in healthy controls and 100% in patients. PIN1 rs2233679 genotype CT/TT may be a risk factor of early cervical cancer compared with genotype CC in Hunan populations. Our findings suggest that PIN1 rs2233679 genotype CT/TT might involve in the progression of the precancerous stage developing to early cancer by enhancing PIN1 expression.

Telomere length in leukocytes and cervical smears of women with high-risk human papillomavirus (HR HPV) infection

Persistent high-risk HPV (HR HPV) infection leads to the development of squamous intraepithelial lesions, which in turn may progress to cervical cancer. Telomere elongation or shortening may indicate a carcinogenesis process. In the present study, we analyzed telomere length from blood and cervical smears of women without and with high-risk HPV infection. Telomere length was quantified by real-time PCR in blood and cervical smears from 48 women with high-risk HPV infection and HGSIL or LGSIL, 29 women HR-HPV positive without SIL, and 11 HPV-negative women. No correlation was found between age and telomere length in blood and cervical smears. Women with high-risk HPV infection had shorter telomeres in cervical smears, but not in blood compared to the control group. These findings suggest that telomere shortening occurs in cervical cells of women with HR HPV infection both with LGSIL and HGSIL and may indicate the onset of carcinogenesis. In turn, there is no correlation between leukocyte telomere length and cervical cancer risk in women with HR HPV infection.

Standardization and experience may influence the survival of laparoscopic radical hysterectomy for cervical cancer

Minimally invasive radical hysterectomy has been shown to be associated with poorer outcome in an influential prospective, randomized trial. However, many centers worldwide performing minimally invasive radical hysterectomy have data and experience that prove otherwise. We aim to review surgical and oncologic outcomes of patients operated by Laparoscopic Radical Hysterectomy in a tertiary hospital, by experienced surgeons and standardization in radicality, for cervical carcinoma Stage 1A1-1B1 from January 2009 to May 2014. Standardised surgical technique with Parametrium & Paracolpium resection approach was adopted by qualified and experienced Gynecologic/Gyne-Oncologic Endoscopic & Minimally Invasive Surgeons in performing Laparoscopic Radical Hysterectomy for Cervical Cancer stage 1A1-1B1 from January 2009-May 2014, involving 53 patients. Electronic Medical Record system (EMR) Of Chang Gung Memorial Hospital(Tertiary Referral Centre), Department of Obstetrics & Gynecology was accessed for surgical and oncologic outcomes. Fifty-Three patients operated from January 2009 to May 2014 were followed up for an average of 96.7 months with longest follow-up at 127 months. There were no cases of recurrence or death reported. 5 Year - Survival Rate and 5 Year Disease-Free Survival Rate were 100%. Two patients received post-operative pelvic radiation concurrent with chemotherapy using Cisplatin due to greater than 1/3 cervical stromal invasion. It is vital to standardize minimally invasive surgical techniques for early stage cervical cancer, with focus on adequate radicality and resection which may contribute to excellent survival outcomes. Further international multi-center randomized trial (Minimally Invasive Therapy Versus Open Radical Hysterectomy In Cervical Cancer) will provide justification for continued practice of MIS in early stage cervical cancer.

Decreased expression of CLCA2 and the correlating with immune infiltrates in patients with cervical squamous cell carcinoma: A bioinformatics analysis

Calcium-activated chloride channel 2 (CLCA2) is closely related to the invasion, metastasis, and prognosis of some common malignant tumors. The present study aimed to evaluate the role of CLCA2 in cervical squamous cell carcinoma (CESC) using bioinformatics analysis. The mRNA sequencing data and the corresponding clinical data were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database respectively. Then univariate analysis of variance was used to analyze the differential mRNA expression of CLCA2 between normal, cervical Intraepithelial neoplasia (CIN), and CESC tissues and clinicopathological characteristics. The Gene Expression Profiling Interactive Analysis (GEPIA) was used to assess the association between CLCA2 and Disease-Free Survival (DFS), overall survival (OS). The Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. The Tumor Immune Estimation Resource (TIMER) was used to predict the potential biological roles of CLCA2 in tumor-immune of CESC. CLCA2 expression was significantly decreased in CESC tissues compared with normal and CIN tissues (P  0.05). The survival analysis indicated that for DFS, CESC with high CLCA2 expression was associated with better prognoses compared with those with low expression levels (P < 0.05). But for the OS, there was no difference. GSEA revealed that 4 pathways exhibited significant differential enrichment in the CLCA2 high-expression phenotype, including the P53 signaling pathway, the ERBB signaling pathway, the NOTCH signaling pathway, and the ubiquitin-mediated proteolysis. The TIMER reveals the expression of CLCA2 showed a significant inverse association with the number of B cells, Macrophage cells, and Dendritic Cell infiltration. The present study indicates that CLCA2 expression may be a potential prognostic marker for patients with CESC.

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.

Psychiatric problems of anxiety and depression disorder are associated with medical service utilization and survival among patients with cervical cancer

There are few nationwide studies regarding the long-term analysis of cervical cancer patients in Taiwan. Thus, this study aimed to evaluate medical service utilization, and survival among cervical cancer patients initially diagnosed with or without anxiety and/or depressive disorders. This was a retrospective longitudinal study using data from the National Health Insurance Research Database from 1996 to 2010. The study subjects were cervical cancer patients identified by ICD-9-CM codes 180.X, while subjects with anxiety and/or depressive disorders were identified using the following codes: 300.0X-300.9X (minus 300.4X) for anxiety disorder, and 296.2X, 296.3X, 300.4, and 311.X for depressive disorder. The cervical patients with anxiety or/and depression disorder were classified as anxiety/depression (AD) group or the non-disorder (ND) group. Propensity score matching (PSM) was used to adjust for differences between the AD and ND groups. T-tests were used to evaluate differences in medical utilization and the Kaplan-Meier method was used to evaluate survival conditions between the two groups. Statistical analyses were performed using SPSS Statistics 20.0. A total of 3664 patients were identified, with 862 (23.5%) having anxiety, 149 (4.1%) with depression, and 349 (9.5%) having both anxiety and depression. In total, 1360 cervical cancer patients had anxiety/depression disorders. After PSM, the AD group had significantly more outpatient department (OPD) visits than the ND group (p < 0.001) but the survival status was better in the AD group than the ND group (p < 0.001). Cervical cancer patients with anxiety/depression disorders visited the OPD more frequently than those without anxiety/depression disorders but had better survival status. Gynecologists should also consider cancer patients' mental status during follow-up, referring patients to psychiatric professionals for appropriate psychiatric care if appropriate.

Inguinal nodal metastatic squamous cell carcinoma of unknown primary (CUP) detected 7 years before the diagnosis of vulvar squamous cell carcinoma: A case report

Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary. A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events. According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

Acquired lymphangioma circumscriptum of the vulva (secondary to lymphatic obstruction) occurring ten years after a hysterectomy and radiotherapy: A case report

Effectual surgical perineal reconstruction of malignant mucosal vulvar melanoma

To demonstrate a successful surgical treatment and reconstruction in a case of malignant mucosal vulvar melanoma. A 52-year-old woman had stage II bulky malignant mucosal vulvar melanoma and received wide surgical excision with partial vulvectomy. She underwent 2-steps reconstructive vulvoplasty and vaginoplasty with skin grafting 1 year after initial surgical treatment. There was no evidence of recurrence after 3 years of follow-up. Vulvar melanoma is a rare malignant neoplasm. Wide local excision with reconstruction can relieve pelvic discomfort and restore local function after the surgery.

Vulvar epithelioid sarcoma: A case report with literature review

To report a case of vulvar epithelioid sarcoma, a rare type of tumor that has been reported in 37 cases in the English literature to date. We report three cases of vulvar epithelioid sarcoma, proximal type. Wide excisions of the mass were performed with margins free of tumor in all three cases. Due to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. Locoregional lymph node involvement, vascular invasion, tumor size larger than 2 cm, deep localization, presence of necrosis, and a high mitotic index are known as poor prognostic factors. Adjuvant radiotherapy is advisable in the presence of a high-grade tumor or positive margins. The beneficial effect of adjuvant chemotherapy is not well established. Treatment decisions should be made based on the individual case presentation and pathology evaluation.

Re-classification of uterine cervical cancer cases treated with radical hysterectomy based on the 2018 FIGO staging system

We re-classified patients with stage IB-II disease (based on the 2008 system) and compared the outcomes with those obtained after using the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. We reviewed the data of 154 patients with cervical cancer who underwent radical hysterectomy at our hospital during 2006-2016. Pathological, histological, and radiographic data were used to re-classify the cases based on the 2018 FIGO system. We compared these outcomes to those obtained after using the 2008 FIGO assignments. Overall survival (OS) was calculated from primary therapy initiation until death or the last follow-up examination. The histological types were squamous cell carcinoma (108 cases) and others (46 cases). The 2008 FIGO system assignments were stage IB1, IB2, IIA1, IIA2, and IIB (87, 27, seven, five, and 28 patients, respectively). The new 2018 FIGO system assignments were stage IB1, IB2, IB3, IIA1, IIA2, IIB, and IIIC1 (52, 26, 16, six, three, 21, and 30 patients, respectively). Re-classification to stage IIIC1 disease was observed for previously assigned stage IB1, IB2, IIA1, IIA2, and IIB cases (10, seven, two, two, and nine cases, respectively). The median OS durations based on the 2018 FIGO system were 71.7, 61.1, and 62.3 months for patients with stage IB1, IB2, and IB3 (p = 0.04) disease, respectively. The new stage IB3/IIA2/IIB cases had longer OS than the old stage IB2/IIA2/IIB cases. A positive computed tomography (CT) finding of nodal involvement was observed in 37% of cases with pathological confirmation of pelvic lymph node (LN) involvement. Using CT to identify pelvic LN metastasis had a sensitivity of 37% and specificity of 93%. The 2018 FIGO staging system for cervical cancer after radical hysterectomy showed a better ability to differentiate survival outcomes. However, the image evaluation method should be reconsidered.

Besides the front-line maintenance therapy, is any positive impact of poly (ADP-ribose) polymerase (PARP) inhibitors on recurrent high-grade ovarian cancer?

Efficacy and safety of rucaparib in patients with recurrent high-grade ovarian carcinoma: A systematic review and meta-analysis

Ovarian cancer stands as the third most prevalent gynecological malignancy. The advent of PARP inhibitors, particularly rucaparib, has revolutionized the landscape of advanced ovarian cancer treatment, demonstrating notable efficacy with minimal toxicity, especially in patients not previously exposed to PARP inhibitors. Rucaparib's precision-driven approach, targeting specific genetic mutations, disrupts DNA repair mechanisms, resulting in cytotoxic effects on neoplastic cells. This comprehensive review delves into the clinical efficacy and safety profile of rucaparib in recurrent ovarian cancer, showcasing its promising therapeutic approach. A systematic search of studies reporting rucaparib efficacy and safety, up to September 2023, was conducted across various reputable databases and sources. The meta-analysis of seven articles revealed a pooled objective response rate (ORR) of 0.331 (95% CI, 0.221-0.449; I2 = 92.4%), underscoring rucaparib's efficacy, particularly evident in the BRCA-mutated cohort. Rucaparib consistently outperformed controls in progression-free survival (PFS) and overall survival (OS). Safety evaluations indicated that 98.7% of patients experienced treatment-emergent adverse events (TEAEs), with 61% being grade ≥3. Notable TEAEs included nausea (69.0%), fatigue (66.8%), vomiting (37.3%), and constipation (32.1%). Hematological concerns comprised anemia (47.9%), thrombocytopenia, elevated AST/ALT (37.3%), and serum creatinine levels (19.7%). Despite favourable outcomes, the rucaparib group recorded higher event rates across various metrics than controls. The findings underscore the need for meticulous monitoring and dose adjustments to optimize therapeutic outcomes and mitigate the increased risks associated with adverse events. International Prospective Register of Systematic Review Identifier: CRD42023459646.

Reply to “glycosylation of FSH and cancer”

Evolving treatment paradigms for platinum-resistant ovarian cancer: An update narrative review

Platinum-resistant ovarian cancer (PROC) refers to disease progression within 6 months after the completion of platinum-based chemotherapy. Historically, treatment options for PROC were limited with a poor prognosis and non-platinum single agent plus bevacizumab has been the mainstay of treatment. Fortunately, there have been notable advancements in recent years, leading to an advance in treatment paradigms for this challenging disease. Various combinations of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy are being explored for an improved treatment outcome. Antibody-drug conjugates targeting folate receptor alpha, which deliver a cytotoxic payload directly to cancer cells, have emerged as a promising therapeutic approach for PROC. WEE1 inhibitors, such as adavosertib, function by inhibiting the WEE1 kinase activity, leading to premature entry of a cell into mitosis phase and thus increased DNA damage. It has been observed that cancer cells with TP53 mutations may be more sensitive to WEE1 inhibitors. Biomarker testing such as analysis of the expression level of folate receptor alpha or mutation in TP53 may be applicable for identifying patients who are more likely to respond to the specific therapy, enabling a more personalized treatment approach. This overview summarizes key clinical findings on the efficacy and safety of theses novel biomarker-driven therapeutic approaches.

Front-line chemoimmunotherapy for treating epithelial ovarian cancer: Part II promising results of phase 2 study of paclitaxel-carboplatin-oregovomab regimen

In the Part I, we have discussed the background of CA125 and the development of anti-CA125 monoclonal antibody (MAb) to highlight the potential role of CA125 and anti-CA125 MAb in the management of women with advanced stage epithelial ovarian cancer (EOC). Glycosylation change either by N-link or by O-link of CA125 is supposed to play a role in the modification of immunity. Anti-CA125 MAb, which can be classified as OC 125-like Abs, M11-like Abs, and OV197-like Abs, is often used for diagnosing, screening, monitoring and detecting the mesothelin-related diseases of the abdominal cavity, particular for those women with EOC. Additionally, anti-CA125 MAb also plays a therapeutic role, named as OvaRex MAb-B43.13 (oregovomab), which has also been extensively reviewed in the Part I review article. The main mechanisms include (a) forming CA125 immune complexes to activate the antigen-presenting cells; (b) triggering induction of CA125-specific immune responses, including anti-CA125 Abs against various epitopes and CA125-specific B and T cell responses; and (c) triggering CD4 and CD8 T-cell responses specific for B43.13 to produce specific and non-specific immune response. With success in vitro, in vivo and in primitive studies, phase II study was conducted to test the effectiveness of chemoimmunotherapy (CIT) for the management of EOC patients. In the 97 EOC patients after optimal debulking surgery (residual tumor <1 cm or no gross residual tumor), patients treated with CIT had a dramatical and statistically significant improvement of both progression-free survival (PFS) and overall survival (OS) compared to those treated with chemotherapy alone with a median PFS of 41.8 months versus 12.2 months (hazard ratio [HR] 0.46, 95 % confidence interval [CI] 0.28-0.7) and OS not yet been reached (NE) versus 42.3 months (HR 0.35, 95 % CI 0.16-0.74), respectively. The current review as Part II will explore the possibility of using CIT as front-line therapy in the management of advanced-stage EOC patients after maximal cytoreductive surgery based on the evidence by many phase 2 studies.

Ovarian clear cell carcinoma with uterine intramural recurrence: Case report of ovarian clear cell carcinoma with fertility sparing treatment

Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.

Comment on the safety and feasibility of no-placement of urinary catheter after single-port laparoscopic surgery in patients with benign ovarian tumor: A retrospective cohort study

Association of immunohistochemical profiles with histotypes in endometrial carcinomas

Although a large number of endometrial cancer patients are cured with surgery alone, there are significant numbers of patients with more aggressive variants of endometrial carcinoma for whom the prognosis remains poor. We investigated the effects of prevalence, histotypes, and immunohistochemical profiles on prognostic value in a hospital-based population. A retrospective study of surgically resected primary endometrial carcinoma was included. Immunohistochemical stains were performed on formalin-fixed paraffin-embedded tissue microarray sections for β-Catenin, estrogen receptor (ER), progesterone receptor (PR), HER-2, MLH1, MSH2, MSH6, PMS2, and p53. Loss of mismatch repair expression was detected in 25.4% of samples (29/114, mean age 57 years) of the tumors. The following loss of expression was observed in patients: MLH1/PMS2 in 16.6% of patients, MSH6 in 7.0% of patients, MLH1 in 0.9% of patients, and MSH6/PMS2/MLH1 in 0.9% of patients. Immunohistochemistry of p53 was analyzed for 111 patients. A total of 13 patients (11.7%, mean age 64 years) had p53-abnormal expression (absent, cytoplasmic or diffuse strong positive patterns), and more than half (9/13, 69.2%) had endometrioid histotype. Abnormalities in p53 were significantly associated with histotype (p = 0.001), advanced tumor stage (p = 0.038), death of disease (p = 0.002), PR percentage (p = 0.002), and HER-2 expression (p = 0.018). Immunohistochemical nuclear localization of β-Catenin was detected in 7.1% of the cohort. The combination of p53 and nuclear β-Catenin expressions was not significantly predictive of disease-free or overall survival. The results of this study are useful for management of endometrial cancer in patients with DNA mismatch repair, abnormal p53 expression, or nuclear localization of β-Catenin.

Sentinel-lymph-node mapping in endometrial cancer: Tumor location matters?

Precise lymph node biopsy for endometrial cancer confined to the uterus: Analysis of 43 clinical cases

To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07-2019.09) and stage II (2019.09-2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.

Sarcopenia in patients with endometrial cancer treated with chemotherapy is correlated with febrile neutropenia

Sarcopenia, characterized by reduced skeletal muscle mass, may impact chemotherapy tolerance and outcomes in cancer patients. In this study we aimed to investigate the correlation of sarcopenia with chemotherapy-related complications and oncological outcomes in patients with endometrial cancer. We retrospectively collected data from the electronic medical records of patients who underwent chemotherapy from January 2015 to August 2021. We measured the L3 vertebral skeletal muscle index (L3SMI), using the abdominopelvic computerized tomography and sarcopenia was defined as an L3SMI of <41 cm A total of 117 patients underwent chemotherapy at our hospital, and 97 patients were included in our study (n = 28 and 69 patients in the sarcopenia and non-sarcopenia groups, respectively). The body mass index of patients in the sarcopenia group was lower than that of patients in the non-sarcopenia group (22.55 ± 2.38 vs. 26.85 ± 4.52 kg/m Patients with endometrial cancer and sarcopenia who underwent chemotherapy showed increased chemotherapy-related complications, such as febrile neutropenia. These findings suggest the need for close monitoring of sarcopenic patients and consideration of prophylactic measures, such as granulocyte-colony stimulating factor administration.

Identification of novel molecular subtypes of endometrial cancer based on neutrophil-related genes to assess prognosis and immune landscape

Endometrial cancer (EC) exhibits significant heterogeneity in clinical outcomes, and neutrophils are increasingly implicated in its progression and the tumor microenvironment. The objective of this research was to discover neutrophil-associated genes in EC and construct a prognostic model along with biologically distinct molecular subtypes. Data on clinical features and gene expression obtained from the Cancer Genome Atlas (TCGA) were subjected to analysis. To identify prognostic markers, we applied univariate Cox regression combined with several machine learning approaches, including least absolute shrinkage and selection operator (LASSO) regression, Random Forest (RF), and extreme gradient boosting (XGBoost), to screen for prognostic neutrophil-related genes. To classify molecular subtypes, we applied non-negative matrix factorization (NMF) on the gene expression data. Using the selected genes, a risk score model was formulated. We established a nomogram for predicting the clinical outcome of EC. Validation of the model was carried out on datasets from internal and external sources. We characterized the risk groups and molecular subtypes using CIBERSORT, ESTIMATE, and Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithms to investigate immune cell infiltration along with immune-related functional pathways. Additionally, we investigated the potential responsiveness to drugs linked to the identified genes and risk categories. We identified four key neutrophil-related genes, including LEF1, GHH, CCL22, and PLA2G2A, which constitute a robust prognostic biomarker set for EC. Based on these genes, the risk score distinguished patients into distinct high- and low-risk categories with markedly different overall survival outcomes. Furthermore, NMF analysis revealed two distinct molecular subtypes based on these four genes, which displayed significant differences in prognosis and were characterized by unique infiltration of immune cells and expression levels of immune checkpoints. We also observed associations between the risk groups and potential drug sensitivities. In this research, we discovered a novel prognostic signature comprising four genes and classified EC into two distinct molecular subtypes driven by neutrophil-associated genes. These results enhance our understanding of EC's prognostic profile and its immune microenvironment, which may facilitate improved risk stratification and guide the design of personalized treatment approaches.

Molecular subtyping and the 2023 FIGO staging in endometrial cancer: Redefining adjuvant therapy

The 2023 update to the FIGO staging system for endometrial cancer has introduced important changes, particularly in classifying early disease, which now more effectively aligns with histological types and molecular profiles to guide treatment strategies. In recent years, molecular classification, including the identification of POLE mutations, mismatch repair deficiency (dMMR), and p53 abnormalities, has become essential in tailoring adjuvant therapies for patients with endometrial cancer. Women with new FIGO stage I non-TP53-mutated tumors, and stage I/II POLE-mutated tumors generally have excellent outcomes, and adjuvant therapy is typically not recommended. In contrast to the established adjuvant treatment of stage IIB disease, controversy surrounds the treatment of stage IIA and IIC patients without POLE mutations. Real-world data suggest that adjuvant radiotherapy or chemotherapy may offer no significant benefit compared to observation in these cases. For stage III POLE-mutated tumors, studies have demonstrated favorable prognoses and high salvage rates upon recurrence, raising important questions about the necessity of adjuvant treatment when complete surgical resection is achieved. For stage III/IV dMMR patients, immune checkpoint inhibitors have demonstrated substantial improvements in both progression-free survival and overall survival when added to chemotherapy, as shown in the RUBY, NRG-GY018, AtTEnd, and ENGOT-en11/GOG-3053/KEYNOTE-B21 trials. These findings have solidified the use of immunotherapy in this molecular subgroup. In the non-specific molecular profile group, hormone receptor status has emerged as a significant prognostic marker. Estrogen receptor-positive tumors in this subgroup have shown favorable responses to progestin therapy, raising the possibility that hormonal therapy could replace chemotherapy in selected patients. Lastly, patients with TP53-mutated tumors, which are associated with poor prognosis, are being evaluated in the RAINBO p53abn-RED trial to assess whether the addition of olaparib to adjuvant chemoradiation can improve outcomes in this high-risk group. In conclusion, integrating molecular subtyping with the 2023 FIGO staging system is reshaping the approach to adjuvant therapy in endometrial cancer, enabling more precise and individualized treatment strategies that improve patient outcomes.

Expected treatment for endometrial polyp

Para-aortic lymphadenectomy in endometrial cancer patients with left-sided inferior vena cava: A case report and literature review

The incidence of left-sided inferior vena cava (IVC) is extremely low. However, without a preoperative diagnosis of left-sided IVC, the risk of intraoperative vascular injury during para-aortic lymph node (PAN) lymphadenectomy is high. Herein, we present two cases in which left-sided IVCs were diagnosed using preoperative imaging. PAN lymphadenectomies were safely performed in these patients with endometrial cancer. In the first case, the left-sided IVC crossed the abdominal aorta after the left renal and gonadal veins had drained into it and joined the right renal vein. In the second case, the left-sided IVC crossed the abdominal aorta after the left renal and gonadal veins flowed into it and the ascending lumbar vein flowed into the right side. These cases demonstrate that even in the presence of vascular malformations, PAN lymphadenectomy can be performed safely by employing preoperative anatomical imaging analysis and judicious intraoperative surgical maneuvers to avoid vascular injury.

Endometrial cancer: Part II. Multimodality treatment of uterine high-grade serous carcinoma (clinical course II)

The part II (clinical course I) of endometrial cancer (EC) describing the complex clinical course (initial treatment and therapy for the first recurrence at both local-regional and distant metastatic sites) of a 66-year-old woman with uterine high-grade serous carcinoma (HGSC, post-curettage diagnosis) after minimally invasive surgery (MIS) treatment-confirmed absence of residual tumor. In the clinical course I, we discussed the recent trend in using MIS for treating early-stage EC patients, regardless whether histologic types are classified, as well as the rationale of absent following postoperative adjuvant therapy due to no residual tumor of gross specimen after complete staging surgery. The patient had multiple recurrences at both loco-regional and distant sites after 22-month disease-free survival (DFS). After salvage therapy, including incomplete cytoreductive surgery for symptom control, chemotherapy, radiotherapy and final systemic therapy, the patient had a durable response period (10-month treatment plus 9 months of the 2nd progression-free survival [PFS]). The current report is the subsequent clinical course of this patient (clinical course II), which further managed this patient at the second recurrence based on multiple modality treatment to achieve the durable response and significantly improve the quality of life.

Complete remission of endometrial cancer stage IVC treated with multimodality treatment including immunotherapy and maintenance PARP inhibitor – A case report

Mismatched repair (MMR) deficient, stage IVC endometrial carcinoma (EC) are occasionally reported as cured by immune-checkpoint inhibitors (ICIs). We present an MMR proficient (MMRp) case with long-term survival. The patient was diagnosed with EC (endometrioid, grade 3, MMRp, programmed death-ligand 1 positive) stage IVC (lung, spine/pelvic bone, paraaortic, pelvic, inguinal and presacral node metastases) with tumor extended from endometrium to cervix, vagina to vulva. After responded to chemoimmunotherapy with paclitaxel/carboplatin then liposomal doxorubicin/carboplatin, pembrolizumab and radiotherapy to pelvis/pelvic bone metastasis, the patient received definitive surgery which showed only residual EC. Olaparib was used as maintenance therapy. The patient developed isolated recurrence in presacral lymph node 2.5 years later, she underwent proton therapy and got complete remission again and maintained with olaparib. She is currently without disease 31 months since recurrence. Initial stage IVC MMRp EC with recurrence is still potentially curable with multimodality treatment including ICI.

Primary endometrial squamous cell carcinoma (PESCC): Review of the literature and case report

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare type of endometrial cancer with limited research and understanding. This report presents a case of PESCC and reviews 37 cases from 1997. A 61-year-old menopausal woman presented with abnormal vaginal bleeding. Despite no prior Papanicolaou smears and normal Pap results this time, transvaginal sonography revealed 7 mm endometrial thickening and elevated cancer antigen 125 (CA-125). Dilatation and curettage revealed atypical glands with squamous metaplasia. On May 3, 2017, she underwent robot-assisted staging surgery (stage IB) and pelvic radiotherapy. No disease recurrence observed till now. Early diagnosis of PESCC is crucial for management. Although guidelines are lacking due to the rarity of PESCC, increased reporting and research are expected to shed light on this condition and facilitate the establishment of treatment protocols.

Endometrial thickness in tamoxifen-treated women

Integrating molecular pathology to endometrial cancer

Good outcome of endometrial cancer patients coexisting with adenomyosis is a result of their associated favorable clinico-pathological parameters

The role of sialylation in gynecologic cancers

Sialic acids (SA) are a kind of nine-carbon backbone sugars, serving as important molecules in cell-to-cell or cell-to-extra-cellular matrix interaction mediated by either O-linked glycosylation or N-linked glycosylation to attach the terminal end of glycans, glycoproteins, and glycolipids. All processes need a balance between sialylation by sialyltransferase (STs) and desialylation by sialidases (also known as neuraminidases, NEU). Although there is much in uncertainty whether the sialyation plays in cancer development and progression, at least four mechanisms are proposed, including surveillance of immune system, modification of cellular apoptosis and cell death, alteration of cellular surface of cancer cells and tumor associated microenvironment responsible carcinogenesis, growth and metastases. The current review focuses on the role of glycosylation in gynecologic organ-related cancers, such as ovarian cancer, cervical and endometrial cancer. Evidence shows that sialylation involving in the alternation of surface components of cells (tumor and cells in the microenvironment of host) plays an important role for carcinogenesis (escape from immunosurveillance) and dissemination (metastasis) (sloughing from the original site of cancer, migration into the circulation system, extravasation from the circulatory system to the distant site and finally deposition and establishment on the new growth lesion to complete the metastatic process). Additionally, modification of glycosylation can enhance or alleviate the aggressive characteristics of the cancer behaviors. All suggest that more understandings of glycosylation on cancers may provide a new therapeutic field to assist the cancer treatment in the near future.

Effect of coexisting adenomyosis on tumour characteristics and prognosis of endometrial cancer: A systematic review and meta-analysis

To compare clinicopathological features and survival outcomes in patients with endometrial cancer, with and without associated adenomyosis. PubMed, Embase and Scopus databases were systematically searched for relevant observational studies. The pooled effect sizes were reported as either hazards ratio (HR) for survival-related outcomes or as odds ratio (OR) for other categorical outcomes. Weighted mean difference (WMD) was reported for continuous outcomes. All the analyses used the random effects model. A total of 21 studies (N = 46,420) were included. Compared to endometrial cancer patients without adenomyosis, patients with associated adenomyosis had improved overall 5-year survival (OS) (HR 0.62, 95% CI: 0.50, 0.79) and disease-free survival (DFS) (HR 0.60, 95% CI: 0.44, 0.82). Disease-specific survival was statistically similar in patients with and without adenomyosis (HR 0.60, 95% CI: 0.35, 1.05). Among patients with adenomyosis, the risk of having an advanced tumour grade (Grade 2 or 3) was lower (OR 0.51, 95% CI: 0.42, 0.62) and a risk of having International Federation of Gynaecology and Obstetrics (FIGO) stage I or II was higher (OR 2.23, 95% CI: 1.65, 3.01). Patients with adenomyosis had lower risk of tumour invasion of adnexa, cervical stromal invasion, deep myometrial involvement (DMI), lympho-vascular space invasion (LVSI) and peritoneal invasion. Presence of adenomyosis in patients with endometrial cancer is associated with favourable tumour characteristics and may improve the survival.

Prognostic factors and survival of endometrial cancer: An 11-year retrospective cohort study in southern Taiwan

Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. In Taiwan, the incidence of EC increased from 1.69 in 1980 to 11.36 per 100,000 women/year in 2010. Therefore, we aimed to study the prognostic factors and survival of patients with EC in southern Taiwan. This study included patients with EC who underwent hysterectomy-based surgery at our hospital between 2010 and 2020. The primary outcome was 5-year progression-free survival (PFS) and overall survival (OS) of patients diagnosed with EC. The secondary outcome was the prognostic factors associated with 5-year PFS and OS in patients with EC. We used the chi-square test to assess categorical variables and the independent t-test to assess continuous variables. The Kaplan-Meier method was used to estimate survival outcomes. Cox regression analysis was conducted to examine the factors associated with PFS and OS. A total of 133 patients were enrolled in this study. The mean age of the patients was 56.5 ± 10.71 years. The mean body mass index was 26.4 ± 5.21 kg/m In conclusion, endometrioid histology was linked to more favorable PFS, while LVSI was related to adverse PFS. Our study did not identify any factors associated with OS. Two-thirds of the patients underwent minimally invasive surgery.

Clinical outcomes in women with endometrial polyps underwent conservative management

To evaluate the regression rate of endometrial polyps (EPs) in a cohort of asymmetric women after conservative follow-up. In this retrospective cohort study, a total of 1006 women with asymptomatic EPs were treated with expectant management or hormonal drugs between June 1999 and May 2018. Four hundred forty-eight women (44.5%) were administered with hormonal medications and 558 women were managed expectantly (55.5%). Office hysteroscopy was performed to confirm the diagnosis and regression of EPs. Hormonal administration included oral contraceptives, progestin and cyclic estrogen/progestin regimen according to physicians' preferences. Clinical characteristics, including the patient's age, body mass index, parity, and type of conservative management were collected. The mean observation time was 14.1 ± 18.5 months (range, 1-162 months). The overall regression rate of EPs in this cohort was 33.5%, 24.6% occurred after medication and 8.9% after expectant management. Patient age (<50 years) (p < 0.001), follow-up period (p = 0.005) and hormonal drugs used (p < 0.001) were significantly associated with EP regression. Twenty-four (7.1%) of the 337 EP regression patients later developed recurrent disease. Follow-up period (p < 0.001) and hormonal drugs used (p = 0.032) were closely related to polyp recurrence after initial regression. Nevertheless, multivariate logistic regression analysis revealed that hormonal drugs used was significantly associated with the regression (p < 0.001) and recurrence (p = 0.016) of EPs. Women aged 50 or less are more suitable for conservative treatment for EPs. Hormonal drugs used could increase the incidence of EP regression.

Evaluation of endometrial thickness in breast cancer patients with tamoxifen treatment – Difference between 2-dimensional ultrasonography and elastosonography

This study aimed to confirm the clinical significance of elastographic endometrium measurement in comparison with conventional ultrasonography for tamoxifen users with breast cancer. In this retrospective analysis, 98 women receiving tamoxifen as postoperative breast cancer treatment were included. Patient medical charts were reviewed, and related medical, obstetric, and gynecological information and histories relevant to breast cancer were evaluated. Patient clinical imaging data included endometrial thickness measurements using both conventional ultrasonography and elastography, and the differences between these two modalities in delta values were statistically analyzed along with possible influencing factors. Endometrial thickness measured using 2-dimensional ultrasonography had a mean value of 5.81 mm (standard deviation [SD] = 3.09), and elastosonography showed a mean value of 3.07 mm (SD = 1.62). A paired t-test was conducted and a significant difference between them was confirmed (P-value <0.001). Logistic regression analysis revealed that age and duration of tamoxifen treatment significantly influenced the degree of difference between endometrial thickness measurements. Elastosonography may be a more successful and useful tool for measuring actual endometrial thickness than generalized 2-dimensional ultrasonography. In clinical cases with limited use of elastosonography and consequent inability for thorough evaluation of endometrial thickness, practitioners should exercise caution in deciding whether or not to adopt invasive diagnostic procedures, such as endometrial curettage, especially for young patients of reproductive age or those with prolonged treatment of breast cancer with tamoxifen.

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome

We aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report. Two women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6. Ovarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.

Endometrial cancer: Part I. Basic concept

Endometrial cancer (EC) has become one of rapidly increasing women's cancers, contributing to the most common cancer of the female genital tract in high- and middle-incomed countries, including Taiwan. In general, EC is believed its favorable outcome; however, high-grade endometrial cancers have a tendency to recur and also have a high risk to be presented as an advanced stage or accompanied with metastatic lesions, which result in a biggest therapeutic challenge. The standard therapy includes complete staging surgery (sentinel node sampling)/optimal debulking surgery, and subsequent adjuvant therapy, by either radiotherapy locally or systemic therapy as chemotherapy or targeted therapy, or in combination or in subsequential strategy is made based on the risk stratification using clinicopathological prognostic factors. All efforts are made to minimize the risk of recurrence and possible therapeutic failure. In this part I, we would like to overview the general background knowledge (basic concept) about the cancer of uterine corpus, and discuss the recent transformation to patients-tailored therapy based on modern molecular technology as the optimal strategy to balance the therapeutic efficacy and treatment-related toxicity. Optimally, it is possible to reach the best benefits.

A novel necroptosis-associated miRNA signature predicting prognosis of endometrial cancer and correlated with immune infiltration

Necroptosis is a form of programmed cell death identified irrelevant to caspases, which plays an important role in the tumorigenesis and development of cancer. MicroRNAs (miRNAs) are important regulators of both necroptosis and cancer. Expression of sixteen necroptosis-associated miRNAs were analyzed in 546 endometrial cancer (EC) tissues and 33 paracancerous samples from the Cancer Genome Atlas (TCGA). Cox regression analysis was used to evaluate the correlations between miRNAs and overall survival. MiRNAs risk score (Mrs) and nomogram were established to assess the potential value of necroptosis-related miRNAs on prognosis. Expression of miRNA-148a-3p in endometrial cancer cells and endometrial epithelial cells was detected by quantitative real-time PCR (qRT-PCR). The targets genes of miR-148a-3p were predicted using miRDB, miRTarBase and TargetScan and the prognostic-related genes were screened. Immune infiltration analysis was conducted to explore the potential mechanism of these target genes. We identified fourteen differentially expressed miRNAs and selected seven miRNAs (miR-15a-5p, miR148a-3p, miR-7-5p, miR-141-3p, miR-200a-5p, miR-223-3p, miR-16-5p) for prognostic-model construction. The area under the curve (AUC) of receiver operating characteristic (ROC) curve for 1-, 2- and 5-year survival were 0.678, 0.652 and 0.656 respectively. Multivariate analysis revealed that the Mrs was an independent prognostic factor considering other risk factors (HR = 1.928, 95% CI = 1.072-3.467, P = 0.028). Among these miRNAs, miRNA-148a-3p was up-regulated in cancer tissues and cells, and Kaplan-Meier analysis showed its significance in overall survival (OS). The target genes, DNAJB4 and PRNP, were associated with poor prognosis and correlated with tumor immune infiltration. Our study constructed a novel necroptosis-associated miRNAs model for prognosis prediction, and DNAJB4 and PRNP may be therapeutic targets for EC.

Molecular pathology and prognosis of endometrial cancer

Molecular profiling of TAM tyrosine kinase receptors and ligands in endometrial carcinoma: An in silico-study

TAM Receptors (TYRO3, AXL, and MerTK) and their ligands on tumor-associated macrophages are promising therapeutic targets for most solid cancers. However, in endometrial cancer, the most common invasive gynecologic malignancy, the TAM receptor-mediated activation pathway, its molecular mechanisms, and its pathophysiology are unknown. The goal of this research; to uncover the comprehensive genetic profile of TAM receptors and ligands in endometrial cancer. Mutation and expression profiles of the Uterine Corpus Endometrial Carcinoma (UCEC) cohort (n = 509) were obtained using bioinformatics tools providing data from The Cancer Genome Atlas (TCGA). PolyPhen-2 and SNAP tools were used to predict the oncogenic/pathogenic properties of the identified mutations for UCEC. STRING network analysis was performed to better understand the functional relationships of the mutant proteins in cellular processes. Furthermore to the mutation profile, gene expression and survival profiles were also determined. Finally, the correlation between target genes and macrophage infiltration was investigated using the tool TIMER. A total of 229 mutations were detected in 6 genes, and 81 missense mutations are pathogenic. In the UCEC cohort, the expression level of MerTK, AXL, GAS6, and PROS1 was statistically significantly lower in the patient group, while the expression level of CD47 was higher in the patient group than in the healthy group (p < 0.01). Protein-protein interaction analysis identified target genes, SRC protein responsible for important cellular mechanisms such as cell proliferation, adhesion and migration, ITGB3, ITGAV and THSB1 proteins involved in endothelial mesenchymal transition and tumor metabolism reprogramming, and FOLR1 involved in DNA replication and damage repair. We believe that TAM receptors and their ligands may be attractive molecular targets for the treatment of endometrial carcinoma because they act as pleiotropic inhibitors of immune cells, effectively regulate phagocytic clearance of apoptotic cells, and make the tumor microenvironment a more suitable niche for the tumour.

A novel CDKN1A-JAZF1 gene fusion in low-grade endometrial stromal sarcoma arising from endometriosis in abdominal wall cesarean section scar: A case report and literature review

We report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma. A 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5' end of exon 1(NM_000389.5) and JAZF1 3' end of exon 5 (NM_175,061,3) was reported in this case. This report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.

Cylindromatosis (CYLD) expression and prognosis of endometrial cancer

Oct-4 induces cisplatin resistance and tumor stem cell-like properties in endometrial carcinoma cells

Research has suggested that tumor-initiating tumor stem cells are derived from normal stem cells and that tumor cells undergo progressive de-differentiation to achieve a stem cell-like state. Tumor stem cells are characterized by high proliferation ability, high plasticity, expression of multi-drug resistance proteins, and the ability to seed new tumors. Octamer-binding transcription factor 4 (Oct-4) and its activation targets are overexpressed in the tumor stem cells of various types of tumors, and this expression is associated with the pathogenesis, development, and poor prognosis of tumors. The primary objective of this study was to test if a stably transfected with Oct-4 gene cell line, RL95-2/Oct-4, has the characteristics of tumor stem cells. Human endometrial carcinoma cells (RL95-2) were transfected with a plasmid carrying genes for Oct-4 and green fluorescent protein (GFP). The stably transfected cells, RL95-2/Oct-4, were selected using G418 and observed to express the GFP reporter gene under the control of the Oct-4 promoter. GFP expression levels of RL95-2/Oct-4 cells were measured using flow cytometry. The proliferation potential of cells was determined according to cumulative population doubling and colony-formation efficiency. Gene expression was analyzed using reverse transcription-polymerase chain reaction. RL95-2/Oct-4 cells not only exhibited increased expression of the three most important stem cell genes, Oct-4, Nanog, and Sox2, but also had increased expression of the endometrial tumor stem cell genes CD133 and ALDH1. Furthermore, enhanced expression of these genes in the RL95-2/Oct-4 cells was associated with higher colony-forming ability and growth rate than in parental RL95-2 cells. We also observed that cisplatin induced less cell death in RL95-2/Oct-4 cells than in RL95-2 cells, indicating that RL95-2/Oct-4 cells were more resistant to chemotherapeutic agents. The study findings contribute to investigate the effects of Oct-4 on tumor stem cell origins.

Primary fallopian tube cancer mimics endometrial cancer: A diagnostic challenge

The diagnostic accuracy of 3D ultrasound compared to 2D ultrasound and MRI in the assessment of deep myometrial invasion in endometrial cancer patients: A systematic review

Endometrial cancer is a common malignancy in women worldwide, with myometrial invasion (MI) being an important prognostic factor, usually assessed via imaging techniques. The aim of this review is to compare the diagnostic accuracy of 3D transvaginal ultrasound (3D-TVUS), a relatively new imaging modality, to that of 2D transvaginal ultrasound (2D-TVUS) and MRI in the prediction of deep myometrial invasion. Relevant articles were sought on MEDLINE/PubMed, Scopus, Web of Science and Wiley Online Library databases. Articles were included if they were primary studies comparing 3D-TVUS to 2D-TVUS and/or MRI in adult endometrial cancer patients, with histopathological confirmation of MI as a reference standard. Ultimately, 7 studies were included, with 714 participants, 242 with deep MI and a mean age of approximately 60 years. 3D-TVUS, 2D-TVUS, MRI and 3D-TVUS-MRI co-evaluation had a pooled sensitivity of 80.4%, 77.6%, 80.7% and 94.6% respectively and a specificity range of 82.8%, 81.6%, 87% and 69.1% respectively. Overall, no statistically significant differences were found in sensitivity and specificity among 3D-TVUS and the other methods, except for a significant increase in sensitivity (p = 0.038) when combined with MRI. This shows that 3D-TVUS is comparable to MRI as far as diagnostic accuracy is concerned, however remains cheaper, less time-consuming and more tolerable, while offering some advantages over 2D-TVUS as well. Therefore 3D-TVUS application in MI assessment seems promising, although more research is required to further assess this finding and ascertain 3D-TVUS's place in endometrial cancer MI assessment.

DNA mismatch repair deficient (dMMR) endometrial cancer

Sentinel node mapping in endometrial cancer: Tips and tricks to improve bilateral detection rate. The sentitricks study, a monocentric experience

The objective of the study is to show some small tricks for bilateral sentinel lymph node (SLN) uptake in endometrial cancer. Each step of the sentinel lymph node technique was analyzed. The cervix was exposed through the use of vaginal valves and by Martin pliers stapling of the anterior cervical lip. Fifty mg Indocyanine Green (ICG) powder was diluted with 10 ml of physiological solution. The spinal needle was marked at 15 mm with a steri-strip. After 20 min from the administration, in case of no LNS identification, an additional 1 ml in the non-detected side was administered in the superficial cervical area. All cervical injections were made by a single (BR) surgeon experienced in oncological gynecology. Fifty patients undergoing sentinel lymph node research for endometrial cancer. The uptake of at least one side of the sentinel node was 98% (49 cases). Forty-six (92%) patients had bilateral lymph node uptake and 3 patients (6%) had unilateral uptake. Only one patient with pelvic and metastatic aortic lymph nodes had no sentinel nodal uptake. Little tricks can increase the bilateral uptake of the SLN up to 92%. The reinjection could be a key element for the success of the SLN technique. Experienced surgeons could certainly play a fundamental role in raising bilateral SLN detection. Further prospective randomized studies are needed to achieve the best SLN infiltration strategy.

LncRNA TUG1 promotes the migration and invasion in type I endometrial carcinoma cells by regulating E–N cadherin switch

Accumulating evidence has demonstrated that lncRNA Taurine-upregulated gene 1 (TUG1) plays an important role in regulation of cell morphology, migration, proliferation and apoptosis. Our aim was to evaluate the oncogenic role of TUG1 in type I Endometrial Carcinoma (EC) and explore the precise mechanism of TUG1 involved in tumor progression. The GSE17025 data set was used to analyze the correlation of TUG1 expression with type I EC patients' prognosis. Furthermore, TUG1 expression profiles were measured by qRT-PCR from carcinoma tissues and adjacent nonneoplastic tissues (NNT) of 105 type I EC patients. The regulation of epithelial-mesenchymal transition (EMT) related molecules, p-AKT and AKT by TUG1 knockdown was investigated using Western blot analysis; meanwhile, the oncogenic roles of TUG1 were evaluated using cell viability and transwell migration/invasion assay in Hec-1-A and Ishikawa cell lines. Firstly, we observed a significant association between higher TUG1 expression and lower survival rate in type I EC patients using the GSE17025 data set. A significant elevation of TUG1 levels was confirmed in type I EC tissues compared with NNT in the 105 type I EC patients, and high expression of TUG1 was associated with lymph vascular space invasion (LVSI) and lymph node metastasis (LNM). Subsequently, TUG1 knockdown could remarkably inhibit the Hec-1-A and Ishikawa cell invasion and migration in the functional experiment. Furthermore, our results showed that the protein levels of E-cadherin increased and N-cadherin decreased significantly, while β-catenin and Vimentin were not significantly altered upon TUG1 silencing in both Hec-1-A and Ishikawa cells. Finally, we found the p-AKT and AKT protein levels, and the rate of p-AKT/t-AKT has a tendency to be down-regulate in Hec-1-A cells, while the AKT pathway was not change significantly in Ishikawa cells after TUG1 knockdown. Collectively, our data reveal that TUG1 might be regarded as an oncogenic molecule that promotes type I EC cells metastasis leading to tumor progression, at least partially, by regulating E-N cadherin switch and the AKT pathway.

Exceptional widespread, life threatening lung metastasis in stage IA ovarian endometrioid carcinoma: A case report

Low-risk, early stage, ovarian endometrioid carcinoma seems to have little chance to recur in clinical practice. Such a patient developed widespread, life-threatening pulmonary metastases is also extreme rare and is worthy to be reported. A 53-year-old female, who was diagnosed to have stage IA, grade 2, ovarian endometrioid carcinoma, developed a life threatening widespread lung metastasis in 2 years after primary surgery. She received salvage systemic chemotherapy with paclitaxel plus carboplatin. Bevacizumab was added after occurrence of paroxysmal supraventricular tachycardia during chemotherapy. The patient had clinical improvement and radiological stable after systemic therapy. Our case report enhances the aggressive post-operative surveillance including chest field would still be recommended even in the low-risk patients. To detect distant metastases earlier probably has higher chance of cure by systemic therapy.

Isolated rectus abdominis muscle recurrence of endometrial cancer

An incidental diagnosis of endometrial cancer in a young and underweight female with isolated symptom of amenorrhea

We demonstrate a young woman with the incidental diagnosis of endometrial cancer, although all common risk factors of endometrial cancer were absent and endometrial lining in ultrasound was smooth either. A 23-year-old female was referral from local clinic for frequent lower abdominal pain, enlarged right adnexal cystic tumor and suspected adnexal torsion. A special symptom of annual menses (menses around every year) was also complained. The onset of the amenorrhea was 6 years ago just after a laparoscopic salpingostomy for right pyosalpinx. Her body mass index (BMI) was 16.8 kg/m Generally, the clues to detect endometrial neoplasm in a young female include family or genetic predisposition, menstrual patterns of abnormal spotting, obesity, risk of polycystic ovary syndrome and/or bizarre images of endometrial lining. However, the above conditions are all absent in the presenting case except the symptom of amenorrhea, in which the chronic anovulatory status may overstimulate the endometrium from the unopposed estrogen and potentially lead to the malignant transformation. Endometrial tissue assessment would be crucial for any young woman suspected to have prolonged exposure (≥6-12 months) of unopposed estrogenic stimulation. Endometrial tissue sampling in premenopausal group with amenorrhea for more than 6-12 months could not be ignored even for the young patient without common risk factors of endometrial cancer.

Vaginal natural orifice transvaginal endoscopic surgery (vNOTES) surgical staging for endometrial carcinoma: The feasibility of an innovative approach

This study aims to describe the feasibility of treating early-stage endometrial cancer with hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy, and bilateral pelvic lymphadenectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES). A longitudinal study of prospectively registered patients was conducted at an academic tertiary care center. 15 patients who underwent vNOTES surgical staging of early endometrial carcinoma between January 2014 and December 2020 were included in the study. 15 patients between 20 and 80yrs of age with histologically proven Stage1 Gr1-2 endometrial cancer underwent vNOTES surgical staging. The mean age of the study population was 52.8 years (Standard Deviation [SD] 6.8) and the mean BMI was 27.8 kg/m With this study, we studied the feasibility of vNOTES surgery for early-stage endometrial cancer with minimal complications and the best long-term surgical outcome. The surgeries were performed by a single skilled endoscopist surgeon with previous experience with vNOTES surgery for adnexal tumors and hysterectomy. Our results showed the practicality of vNOTES in staging surgery for early-stage endometrial cancer. However, application to a larger cohort is required for more extensive surgical outcome studies.

Effect of primary prophylaxis with pegfilgrastim in endometrial cancer patients treated with doxorubicin and cisplatin

Although the incidence of febrile neutropenia (FN) is relatively higher for doxorubicin and cisplatin combination regimen than for other regimens in endometrial cancer, evidence regarding the efficacy of pegfilgrastim in this regimen is lacking. We retrospectively reviewed the data of 58 patients with endometrial cancer who were treated with doxorubicin plus cisplatin. The patients were divided into primary prophylaxis and non-prophylaxis groups. We compared the incidence of FN and neutropenia as well as the chemotherapy relative dose intensity (RDI) and usage of antibiotics between the groups. The rates of FN (8.0% vs. 34.8%) and grade 4 neutropenia (12.0% vs. 87.0%) were significantly lower in the primary prophylaxis group. Although there was no difference in the RDI between the groups, the primary prophylaxis group had a lower rate of antibiotic prescriptions. Prophylaxis with pegfilgrastim efficiently prevented FN in patients treated with doxorubicin and cisplatin.

High-grade endometrial stromal sarcoma in cesarean section scar isthmocele - case report

Cesarean section scar defect isthmocele, the pouchlike defect in the anterior uterine wall of the prior cesarean site. No previous report of malignant neoplasm in the isthmocele have been published. We reported a case of High-grade endometrial stromal sarcoma in isthmocele. A 45-year-old patient with gravida 4, parity 2, two previous cesarean section presents of recurrent heavy vaginal bleeding. Curettage and hormone therapy were unsuccessful. She underwent hysteroscopic isthmoplasty. The pathology revealed high-grade sarcoma. Patient was referred to a tertiary medical center and she underwent total hysterectomy with bilateral salpingo-oophorectomy, aortic & pelvic LNs dissection. The final diagnosis was High-grade endometrial stromal sarcoma (HG-ESS) stage IA (pT1a N0) involving isthmocele. The presence of this rare tumor in the isthmocele is very interested. We stress the necessity for a high degree of suspicion to diagnose the malignancy in perimenopausal women with isthmocele and persisted abnormal uterine bleeding.

Diagnostic and prognostic value of genomic instability-derived long non-coding RNA signature of endometrial cancer

To investigate whether genomic instability (GI)-derived long non-coding RNAs (lncRNAs) have a prognostic impact on the patients with endometrial cancer. Patients with Uterine Corpus Endometrial Carcinoma (UCEC) were selected from The Cancer Genome Atlas (TCGA) database. Systematic bioinformatics analyses were performed, including Pearson correlations, GO and KEGG enrichment analysis, bivariate and multiple logistic regression analysis, and Kaplan-Meier (KM) method. A total of 552 UCEC samples were included in the study. The differentially expressed lncRNAs (DELs) were identified, including 79 down-regulated lncRNAs and 31 up-regulated lncRNAs. Bivariate logistic regression analysis showed that 19 GI-derived lncRNAs were prognostic factors. By further multivariate logistic regression analysis, AC005256.1 (estimated coefficient = -0.474), AC026336.3 (estimated coefficient = -0.030), AL161618.1 (estimated coefficient = -1.661), and BX322234.1 (estimated coefficient = 1.511) were used to construct a prognostic risk model. In the train set and test set, the risk model was shown to have both a high prognostic and a diagnostic value. We developed a novel GI-derived 4-lncRNA signature for the diagnosis and prognosis of patients with endometrial cancer. These findings offered a novel perspective in the clinical management of endometrial cancer.

Carcinosarcoma arising from high-grade serous carcinoma of the ovary without estrogen receptor, WT-1, and PAX8 immunoreactivity

We encountered a case of high-grade serous carcinoma (HGSC) of the ovary which recurred as carcinosarcoma of the sigmoid colon. Tumor cells of both the primary carcinoma and the secondary carcinosarcoma were negative for estrogen receptor (ER), WT-1, and PAX8. It is well known that most ovarian carcinomas arising from the Müllerian duct are immunoreactive for these biologic parameters. To our knowledge, this is the first case report that provides the results of immunohistochemical analysis of WT-1 and PAX8 for a primary carcinoma and recurrent carcinosarcoma. A 61-year-old woman had an advanced right ovarian HGSC. After a primary debulking surgery (hysterectomy, bilateral salpingo-oophorectomy and omentectomy) and adjuvant chemotherapy, complete remission was achieved. However, four and a half years later, a tumor arising beside the sigmoid colon was detected. A tumorectomy was performed through combined partial resection of the ileum and sigmoid colon. Microscopically, the tumor was diagnosed as carcinosarcoma of the sigmoid colon, which had originated from HGSC of the ovary. Interestingly, the malignant cells of the primary carcinoma and epithelial components of the recurrent carcinosarcoma were negative for ER, WT-1, and PAX8. These immunohistochemical features were unusual. Three cycles of chemotherapy with the previously used regimen and three additional cycles of doxorubicin and ifosfamide combination chemotherapy were administered. Currently, 3 years after the final chemotherapy was administered, the patient remains healthy. HGSC of the ovary can recur as carcinosarcoma. Tumor cells of the primary HGSC without ER, WT-1, and PAX8 expression may have dedifferentiated and recurred as carcinosarcoma.

Endometriosis-associated epithelial ovarian cancer is a more complicated disease than we suspected before

Endometriosis-associated epithelial ovarian cancer (EOC) often includes clear cell carcinoma and endometrioid-type carcinoma. Due to the low incidence of primary mucinous EOC and absence of association between endometriosis and primary mucinous EOC, we present an unusual endometriosis-associated mixed mucinous and endometrioid adenocarcinoma arising from the same ovary. A 54-year-old woman had an abdominal palpable mass for months. Medical and surgical history, as well as preoperative surveys was unremarkable, except of presence of a pelvic mass. She underwent an exploration laparotomy, and a 22-cm right ovarian tumor was found. Grossly, right ovarian tumor containing brownish cloudy cystic fluid 2450 ml and an apparent 4 × 4 × 2 cm-sized papillary growth. Microscopically, a confluent glandular and infiltrative pattern presented endometrioid adenocarcinoma, and cells with intracytoplasmic mucin and stratified elongated epithelial cells presented mucinous adenocarcinoma. Surgico-pathological stage was FIGO IIIA due to tumor invading to the peritoneum above the pelvis. Postoperatively, the dose-dense chemotherapy was applied with uneventful outcome. This is a rare case, composed with mixed mucinous and endometrioid adenocarcinoma of the same ovary, suggesting that careful pathological diagnosis of endometriosis-associated EOC is needed.

Prognostic factors determining survival after extrapelvic recurrence in endometrioid type endometrial cancer

To define the factors that determine survival after extrapelvic recurrence in patients with endometrioid type endometrial cancer (EC).objective MATERIALS AND METHODS: Clinicopathological and survival data of surgically treated endometrioid type EC patients who recurred outside pelvis were reviewed. Patients who had non-endometrioid tumor, sarcomatous component in the final pathology and synchronous tumor were excluded. The period from surgery to recurrence was defined as time to recurrence (TTR) and the period from recurrence to death or last visit was defined as post-recurrence survival (PRS). Sixty-six patients with extrapelvic recurrence were included in the study. No residual disease was achieved in all patients at initial surgery. Median TTR was 18 months (range, 2-84). Recurrence developed within 1 year in 24 (36.4%) patients and between 13 and 24 months in 22 (33.3%) patients. Fifty-three of 66 patients (80.3%) had extraabdominal recurrence. The 2-year PRS of the all cohort with extrapelvic recurrence was 56%. In the univariate analysis, advanced FIGO stage, lymph node metastasis, adnexal metastasis and short TTR were associated with diminished PRS (p < 0.05). The salvage chemotherapy for recurrence had a tendency to be associated with improved PRS in the univariate analysis. Two-year survival was 81% and 37% in the patients who received chemotherapy and radiotherapy, respectively (p = 0.057). Almost half of the patients with extrapelvic recurrence died of disease within 2 years. Chemotherapy seemed to be more effective than radiotherapy as the salvage therapy of extrapelvic recurrences.

Massive metastasis of breast cancer to female genital organs

Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.

Diagnostic value of endometrial volume and flow parameters under 3D ultrasound acquisition in combination with serum CA125 in endometrial lesions

This study aims to discuss the differential diagnosis value of endometrial volume and flow parameters in combination with serum carbohydrate antigen 125 (CA125) in endometrial benign and malignant lesions. The data of 250 patients with endometrial lesions were retrospectively analyzed. Carbohydrate antigen 125 (CA125) was determined before the operation. The morphology, hemodynamics, volume and flow parameters of the endometrium were measured by transvaginal three-dimensional-power Doppler angiography (3D-PDA). The endometrial volume (EV), 3D-PDA vascular index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using the virtual organ computer-aided analysis software (VOCAL). According to the pathological results, 202 patients (80.8%) had benign endometrial lesions and 48 patients (19.2%) had endometrial cancer (EC). The endometrium of EC patients was thicker (15.64 ± 7.26 mm vs. 9.24 ± 5.06 mm, P  0.05). Transvaginal 3D-PDA can clearly show the morphological and hemodynamic characteristics of endometrial lesions, and assist in the detection of EC in combination with serum CA125. This may have important clinical application value.

A modified technique to perform para-aortic lymphadenectomy up to the renal vein

To investigate the safety and feasibility of our modified technique to perform lymph node excision up to the renal vein in cases of gynecological cancer. 87 patients with endometrial or ovarian neoplasms underwent laparoscopic para-aortic lymphadenectomy (LPAL) up to the left renal vein were enrolled prospectively. During surgery, the surgeon was positioned to the right side of the patient and an additional trocar was introduced into the upper right abdomen. The laparoscopic video screen was placed to the side of the patient's head. Three-fan retractor forceps were used to hold up the duodenum and small bowel. The rest of the procedure was the same as conventional LPAL. The median operating time for LPAL was 72 min (range: 40-115 min) and the median estimated blood loss was 45 ml (range: 15-1000 mL). There were two cases of intra-operative vascular injury. The median number of retrieved para-aortic lymph nodes (PALNs) was 18 (range: 10-37). Of the 87 patients, 11 patients had positive PALNs. None of the cases required laparotomy. Our findings demonstrate that our modified LPAL technique is feasible, reproducible, can achieve good exposure and reduces surgical difficulty.

Triple synchronous malignancies of the female genital tract with an advanced stage carcinosarcoma of the uterine cervix: A case report

Endometrial adenocarcinoma initially mistaken as urinary incontinence

The report aims to present a case of endometrial cancer with unusual initial presentation. A literature review is conducted to speculate symptoms presented by endometrial cancer other than vaginal bleeding. A 43-year-old, para 1, lean female suffered from copious watery vaginal discharge that was odorless and colorless for 8 months without any signs of abnormal vaginal bleeding. Preliminary surveys in private clinics with per vaginal examination and Papanicolaou smear were normal. Urinary incontinence was mistakenly impressed. When the patient turned to our center for help as symptoms aggravated, transvaginal sonography revealed hydrometra with papillary endometrium lesions. Hysteroscopy survey with endometrial biopsy revealed endometrial adenocarcinoma. This is a case of endometrial cancer with unusual presentation. Transvaginal sonography and hysteroscopy are easy and sensitive screening tools that should be readily offered to patients with suspicious symptoms.

Fertility preservation in early-stage endometrial cancer and endometrial intraepithelial neoplasia: A single-center experience

The purpose of this study was to define the pregnancy and oncologic outcomes after fertility-sparing treatment of atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and early-stage endometrioid endometrial cancer (EEC). The retrospective cohort study included patients who had applied to Başkent University's Ankara Hospital between January 2007 and October 2018 with either AH/EIN (n: 27; Group A) or EEC (n: 30; Group B), and who had the desire to preserve their fertility. The medical records of all patients included in the study were reviewed retrospectively from the hospital records. There were 2 (7.4%) and 5 (16.7%) recurrences, whereby one patient from Group A and two patients from Group B underwent staging surgery. In Group A, 8 patients attempted pregnancy after their treatment and 4 of them (50%) became pregnant, while 3 of them (37.5%) had a live birth. In Group B, there were 17 patients who wanted to become pregnant following treatment of the disease; 8 of them (47%) became pregnant after treatment, 5 of them (16.6%) had a live birth, 1 experienced intrauterine exitus (at 21st gestational week, 350 g), and 2 currently have ongoing pregnancies. Hysteroscopic resection of visible lesions and full endometrial curettage prior to hormonal therapy as a fertility-preserving approach for women of reproductive age with endometrial malignancies can achieve promising oncologic and obstetric responses.

Risk factors for lymphatic complications following lymphadenectomy in patients with endometrial cancer

Lymph node (LN) metastasis is among the important prognostic factors for survival in endometrial cancer (EC). This study aimed to evaluate the occurrence of lymphatic complications following lymphadenectomy in patients with EC. EC patients were retrospectively evaluated. Lower extremity lymphedema (LEL) and pelvic lymphocele (PL) were evaluated according to the International Society of Lymphology guidelines and the National Cancer Institute Common Terminology Criteria for Adverse Events, respectively. A total of 289 patients were enrolled. Surgery was performed via laparotomy and laparoscopy in 200 (69.2%) and 89 (30.8%) patients, respectively. LEL and PL occurred in 43 (14.9%) and 33 (11.4%) patients, respectively. In multivariate logistic regression analysis, circumflex iliac node (CIN) removal (odds ratio [OR]: 3.22; 95% CI: 1.43-7.98; P = 0.004) was an independent risk factor for LEL, while the surgical approach (OR: 4.46; 95% CI: 1.13-29.9; P = 0.004) was an independent risk factor for PL. CIN dissection was a significant risk factor for LEL, while laparotomy was an independent risk factor for PL compared to laparoscopy in EC patients. This suggests that laparoscopic surgery combined with sentinel lymph node navigation surgery will prevent lymphatic complications in low-risk EC patients.

Endometriosis-associated epithelial ovarian cancer: Primary synchronous different cellular type on each ovary

Endometriosis-associated epithelial ovarian cancer (EOC) is a specific category of EOC, containing either endometrioid or clear cell carcinoma subtype. The characteristic of endometriosis-associated EOC includes an early stage at the diagnosis, presence of single histology type, and better prognosis. The synchronous two subtypes of endometriosis-associated EOC and presentation of far-advanced stage status at the initial diagnosis is rarely reported. We reported a 60-year-old postmenopausal woman with FIGO IA endometriosis-associated endometrioid carcinoma at right ovary and FIGO IVA endometriosis-associated clear cell carcinoma at left ovary, right tube, omentum, lymph node and cytology of pleural effusion and ascites treated with optimal debulking surgery and dose-intensity taxane/platinum based chemotherapy. This case report confirms the long-term concept that clear cell carcinoma has much more aggressive behavior than endometrioid cell carcinoma does, regardless of association of endometriosis or not.

Increased risk of ischemic stroke in cervical cancer patients received radiotherapy: A nationwide population-based study

Chemotherapy, radiotherapy, and surgery have been reported to affect the incidence of ischemic stroke in cervical cancer. However, limited sample size and short-term follow up impair the power of analysis. This study aimed to evaluate the impact of different treatment modalities on risk of ischemic stroke (IS) with national population and long-term follow up. We conducted a nationwide population-based, retrospective cohort study using claims data from Taiwan's National Health Insurance program between 2008 and 2014. Cervical cancer patients aged 20 years or more who underwent surgery alone with oophorectomy (n = 1895) were compared with those who received surgery plus chemotherapy (SCT) (n = 1049), concurrent chemotherapy plus radiotherapy (CCRT) (n = 2631), chemotherapy (C/T) alone (n = 1778), and radiotherapy (RT) alone (n = 580). The follow-up period ranged from 5 to 11 years. The multivariate Cox proportional hazards regression models, Kaplan-Meier product-limit method, and the Gray k-sample test were used to assess the risk of IS. During a median follow-up period of 9.1 years, a total of 258 cases (3.3 %) developed IS with the shortest median time-to-event of 1 year in the RT group. The development of IS had negative impact on patients older than 55 years old (hazard ratio, 2.71; 95 % confidence level, 1.96-3.74). In comparison to surgery alone, the hazard risk of IS risk were 1.92, 1.58, and 3.26 for C/T, CCRT, and RT alone, respectively. When stratified by age older than 55 years, older patients who received RT alone had higher risk in terms of treatment modalities. For comorbidity sub-analysis, the older patients had higher risk of IS particularly in those bearing more than two stroke-related risk factors (6.3 % in 55 y/o). For cervical cancer patients older than 55 years old and/or bearing comorbidities related to IS, the RT alone remains reasonable option and the risk of IS should be cautioned.

Improving the symptoms of dysmenorrhea and menorrhagia of women with adenomyosis and myoma in short- and long-term treatment effectiveness of microwave ablation: A systematic review and meta-analysis

To identify improvement of symptoms of dysmenorrhea and menorrhagia of women who underwent treatment of Microwave ablation for adenomyosis and myoma. 463 articles were searched; 15 were included in the qualitative systematic review, and 13 were quantitively included in the meta-analysis and searched from TAYLOR FRANCIS, SCIENCE DIRECT, COCHRANE LIBRARY, WILLEY ONLINE LIBRARY, PUBMED. A total of 1123 of 652 women were diagnosed with adenomyosis, and 471 women were diagnosed with myoma. Studies were analyzed by pooling the weighted mean difference (WMD) with the 95 % CI in terms of study provided as a mean + (SD) and pooled results assessed with a random effect. Heterogeneity was evaluated using the I2 statistic. Visual analog scale (VAS) score and symptom severity scores (SSS) for adenomyosis was compared to post-microwave ablation (MWA) at 3,6, and 12 months showed significantly different heterogeneity with all statistically significant improved. Health-related quality of Life (HRQL) for adenomyosis were compared to post-MWA at 3,6, and 12 months showed significant improved. Hemoglobin (Hb) level for adenomyosis was compared to post-MWA at 3,6, and 12 months showed significantly different heterogeneity with all statistically significant increased the level of Hb. Hb level for myoma was compared to post-MWA and showed significantly different heterogeneity with no statistically significance. Myoma volumes were compared to post-MWA and showed significantly different heterogeneity with statistically significant reduced. Microwave ablation (MWA) is an effective and safe treatment for women with both adenomyosis and myoma in short- and long-term treatment and significantly improved symptoms and quality of life.

Endometrial carcinoma arising in one horn of a didelphys uterus

Endometrial cancer in uterine anomalies is very rare. Currently, few cases with endometrial cancer coexistent with didelphys uterus are described. We present a case of a patient with carcinoma in one only horn of a didelphys uterus. A 50-year-old woman presented with abnormal uterine bleeding. Uterine anomaly was uncertain on initial clinical examination and pelvic ultrasonography. The MRI study showed double uterus and cervixes, a uterine didelphys was suspected. Preoperative histology from curettage described endometrioid adenocarcinoma. The patient underwent laparoscopic hysterectomy with surgical staging. Macroscopic examination revealed a didelphys uterus, and the final histology confirmed the diagnosis of uterine cancer. The coincidence of uterine malignancies and uterine anomalies is rare; however, it should be aware of uncertain diagnosis and delaying of treatment.

Specific hysteroscopic findings can efficiently distinguish the differences between malignant and benign endometrial polyps

To evaluate differences in hysteroscopic findings between benign endometrial polyps and endometrial cancer. From January 2012 to December 2016, we extracted 179 cases with endometrial polyps from 3066 women who underwent hysteroscopy followed by dilatation and curettage or transcervical resection, with 154 and 25 cases of benign and malignant endometrial polyps, respectively. Clinical characteristics, histopathological and hysteroscopic findings of the women were evaluated retrospectively. The hysteroscopic findings of malignant polyps were hyper-vascular (72%, 18/25), ulcerative (64%, 16/25) and polyps with irregular surfaces (24%, 6/25). In contrast, pedunculate small growths with smooth surfaces were usually seen in the benign endometrial polyps (38.3%, 59/154). Hyper-vascular (OR: 142.6, 95% CI: 25.98-783.4) and polyps with irregular surfaces (OR: 12.02, 95% CI: 1.765-81.83) in hysteroscopic findings were significant strong predictors of endometrial polyps with endometrial cancer. Hysteroscopic findings of ulcerative changes were most strongly associated with a diagnosis of malignant polyps, with sensitivity, specificity, negative (NPV) and positive (PPV) predictive values of 64.0%, 100%, 94.5%, and 100%, respectively. Women with hysteroscopic findings of endometrial polyps with hyper-vascular, ulcerative, and polyps with irregular surfaces had a high likelihood of endometrial cancer. A target biopsy of the polyps with these specific appearances should be performed to exclude malignant lesions.

Frequency of serous tubal intraepithelial carcinoma (STIC) in patients with high grade serous ovarian cancer

Serous tubal intraepithelial carcinoma (STIC) is a known precursor of high-grade serous ovarian cancer (HGSOC). This study aimed to evaluate the proportion of STIC in patients with HGSOC and analyze the STIC-related prognosis in patients with HGSOC. All pathology reports at our institution that included bilateral salpingectomies of patients with HGSOC from January 2013 to December 2018 were reviewed by two experienced pathologists. The specimens from the ovaries and the salpinx including fimbria were examined. We analyzed the correlation between STIC and HGSOC and compared the clinical characteristics and STIC-related prognostic outcomes in patients with HGSOC. Eleven of the 76 cases were STIC. BRCA mutations were found in 16.9% of patients with HGSOC. STIC was observed in 30.0% of patients with BRCA mutations and in 14.3% of patients without BRCA mutations. The incidence of STIC in patients with BRCA mutations was approximately twice that in patients without BRCA mutations; however, the difference was not statistically significant (P = 0.231). Further, the 5-year survival rate of patients without STIC appeared to be high; nevertheless, the difference was not statistically significant (59.7% vs. 47.4%, P = 0.633). Moreover, there was no significant difference in disease-free survival rate according to STIC (36.4% vs. 33.1%, P = 0.956). STIC was identified in patients with HGSOC, and STIC incidence was prominent in HGSOC related to BRCA mutation. Although low frequency, STIC was detected in patients without BRCA mutation. Therefore, prophylactic salpingectomy may be useful for prevention of HGSOC.

Nedaplatin use in patients with hypersensitivity reaction episodes to carboplatin

To evaluate the benefits of nedaplatin treatment in patients with a history of hypersensitivity reactions to carboplatin. We retrospectively reviewed the medical records of patients with ovarian, fallopian, and peritoneal cancers and with a history of hypersensitivity to carboplatin between January 2010 and December 2016 at the Department of Gynecology in the Saitama Medical Center associated with Jichi Medical University. We studied the response rate to treatment with a nedaplatin-based regimen compared to that of a carboplatin regimen. Fisher's exact test was used to determine statistical significance. Thirty-one patients with a past hypersensitivity to carboplatin were treated with nedaplatin-based regimen, while ten patients were treated with other drugs. The response rates in the nedaplatin- and non-nedaplatin-treated patient groups were 71.4% and 30.0%, respectively (P = 0.021). Among all the patients, only one experienced hypersensitivity reaction to nedaplatin. The nedaplatin regimen following hypersensitivity to carboplatin was safe, feasible, and effective in achieving complete or partial response.

Peritoneal well-differentiated papillary mesothelioma coexisting with endometrial adenocarcinoma mimicking peritoneal carcinomatosis: A case report

We present a rare case of well-differentiated papillary mesothelioma (WDPM) found incidentally in a 59-year-old woman with endometrial cancer. A 59-year-old nulliparous obese woman with a past history of hypertension and diabetes mellitus presented with postmenopausal bleeding for 11 months. Two months prior to this admission, an episode of massive vaginal bleeding lasting for a day was noticed by the patient. Hysteroscopy was performed after her visit to our outpatient department. Papillary tumors with active bleeding were found in the uterine cavity. Endometrial biopsy showed adenocarcinoma, endometrioid type characterized by papillary architecture lined by columnar cells with mild nuclear pleomorphism. The patient proceeded to magnetic resonance imaging (MRI), which demonstrated a 6.4 × 5.5 × 4.9 cm intrauterine mass. Her tumor marker levels were elevated (CA 125 87.8 IU/ml, CA19-9160.54 IU/ml). The patient then underwent a staging surgery and final pathology revealed stage IA endometrial cancer. During surgery, multiple nodules were found in the peritoneum, initially considered as tumor metastasis and eventually proved to be WDPM. In conclusion, the simultaneous occurrence of WDPM with endometrial cancer is a rare entity. Although no standardized treatment has been established, WDPMs have a relatively favorable prognosis compared to malignant mesotheliomas.

Functional analysis of PHLDA2 in ovarian cancer: Effects on tumor cell behavior and autophagy

We aimed to explore the effect of PHLDA2 on the biological behavior of ovarian cancer (OC) cell in vitro. Validation of PHLDA2 mRNA expression based on the analysis from GEPIA was performed on clinical OC tissues using qPCR. SiRNA-mediated knockdown of PHLDA2 was conducted in OC cells to investigate its potential functions. Afterwards, cell proliferation, migration, and invasion were examined. Moreover, the autophagy level was assessed by the expression of LC3 and P62. The associated protein expression was determined using Western blot. PHLDA2 was highly expressed in OC tissues and cells. PHLDA2 knockdown repressed the cell viability and clone-forming ability of OC cells. PHLDA2 knockdown inhibited migration and invasion, as well as the protein expression of MMP-9 and MMP-2 in OC cells. Moreover, LC3 expression was elevated and P62 expression was reduced after PHLDA2 knockdown. Western blot detection further showed decreased phosphorylation levels of PI3K, AKT, and mTOR in PHLDA2-knockdown cells. These findings reveal that knockdown of PHLDA2 suppresses OC cell proliferation, migration and invasion, while promoting autophagy and inactivating the PI3K/AKT/mTOR pathway, suggesting that PHLDA2 may contribute to OC progression.

Plasma level of cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) is higher in locally advance cervical cancer

This study is aimed to examine the plasma level of ALDH1 in early and locally advanced cervical cancer (CC) patients and to investigate its association with the presence of prognostic factors for recurrence in early stage. This is a cross-sectional study involving 82 patients with CC (33 patients with early stage IB-IIA and 49 patients with locally advance/LACC stage IIB-IVA) who were admitted to Gynecologic Oncology Clinic, Prof. dr. I G.N.G. Ngoerah Hospital Denpasar from September 2022 to April 2023. Prognostic factors for recurrence were recorded from early-stage CC after radical hysterectomy. Pre-treatment plasma level of ALDH1 was determined using ALDH1 ELISA kit (cat. no. E3259Hu). Plasma level of ALDH1 was significantly higher in patients with LACC as compared to early-stage CC (median: 7.0 vs. 4.3 ng/ml, p 0.05). Increasing plasma level of ALDH1 in CC patients was associated with more advance stage and bulkier tumor mass. Our finding suggests that in the clinical setting, evaluating the plasma level of ALDH1 may aid in assessing the progression of cervical cancer. Future study such as longer-term longitudinal study with larger sample size is needed to explore the association between ALDH1 expression and the clinical response to treatment (e.g., chemoradiation) or risk of recurrence in early-stage CC patients.

Complete mole with co-existing fetus: a rare case report of full-term delivery with favorable maternal and fetal outcomes

To explore the obstetric and oncological outcomes of CHMCF and to give a beneficial reference for the individualized management of the disease and the timing of pregnancy termination. A 25-year-old primipara was diagnosed with CHMCF at 17 weeks of gestation by prenatal ultrasound. Magnetic resonance imaging, genetics and consanguinity identification testing were performed. There were no serious pregnancy complications. At 38 weeks of gestation, a small-for-gestational-age fetus was delivered by cesarean section, and there was no obvious abnormality in postpartum follow-up. CHMCF belongs to paternal diploid twin pregnancy. Ultrasound and magnetic resonance imaging are important methods for early diagnosis. When the fetal karyotype is normal and there is no obvious pregnancy complication, it is feasible to continue pregnancy, and the incidence of GTN is not significantly increased compared with the termination of pregnancy.

Community mobile health clinics’ availability is associated with cervical cancer screening in rural and urban areas: A national cohort study in Taiwan

Despite free cervical screening in Taiwan, by 2022, less than 50 % of eligible women had undergone screening, raising concerns about spatial access to these services. Mobile health clinics (MHCs) have been implemented to improve access to primary care. This study aimed to investigate whether the MHC availability was associated with cervical cancer screening rate in rural and urban Taiwan. This retrospective cohort study used 2016-2019 National Health Insurance Research Database to identify 6,754,863 women aged ≥30 years eligible for cervical cancer screening at 2017. Each individual was followed up for three years using 2017-2019 outpatient claims to assess cervical cancer screening uptake. Primary exposure variables include residence urban/rural classification and MHC availability, categorized by place of residence. Chi-square tests and multivariable logistic regression were used to compare screening across exposure groups. In 2017, MHCs were available to 5 % of urban and 29 % of rural residents. Cervical screening rates were slightly higher in urban areas with versus without MHCs (48.24 % vs 47.99 %; p=.006), but slightly lower in rural areas with MHCs (48.09 % vs 48.32 %; p<0.001). Multivariable regression showed higher odds of screening uptake among women living in urban areas with MHCs, and among women living in rural areas regardless of MHC availability, compared to those in urban areas without MHCs. Cervical cancer screening uptake in Taiwan remained low, with the lowest screening rates in urban areas without MHCs. Expanding the reach and effectiveness of mobile health services might help improve cancer screening rates in Taiwan.

FIGO 2023 staging system predicts not only survival outcome but also recurrence pattern in corpus-confined endometrial cancer patients

Approximately 10-15 % of endometrial cancer patients with tumors confined to the uterus (FIGO 2009 stage I) demonstrate recurrence and the oncologic outcomes are highly related to recurrence patterns. This study aimed to verify whether the FIGO 2023 staging system could discriminate outcomes. Between January 2010 and March 2019, 536 FIGO 2009 stage I patients were eligible for this retrospective cohort study. Patient characteristics and clinicopathological data were retrieved from electronic medical records. The patients were reclassified according to the FIGO 2023 staging criteria. Oncological outcomes included the recurrence rate, recurrence pattern, and overall survival. Among the 536 eligible patients, the (sub)stage migration rate was 23.5 % from the FIGO 2009 to the FIGO 2023 stage system. FIGO 2023 staging system resulted in (sub)stage up-migration, mostly owing to aggressive histological types. A higher recurrence rate was detected in the FIGO 2023 stage II patients (12.3 %) compared to the stage I patients (6.9 %). In comparison to the FIGO 2023 stage I patients, the stage II patients had a higher distant recurrence rate (8.8 % vs. 2.6 %) and poorer overall survival (38.0 vs 69.0 months, p = 0.02). Patients who are upstaged are prone to worse oncological outcomes, including distant recurrence and mortality. Therefore, comprehensive adjuvant treatment strategies based on each FIGO 2023 substage are imperative.

Recent advances in cervical cancer treatment: Innovations from early-stage to advanced disease

This article provides a comprehensive review of recent advancements in cervical cancer treatment, highlighting significant breakthroughs in managing the disease at various stages. Traditional treatments, such as radical surgery for early-stage disease and concurrent chemoradiation (CCRT) for advanced stages, have dominated clinical practice for decades. However, recent phase III studies have challenged these norms, leading to new treatment paradigms. For early-stage cervical cancer, the LACC trial revealed that minimally invasive surgery results in poorer outcomes compared to open surgery, prompting updates in clinical guidelines. Additionally, the SHAPE trial suggested that simple hysterectomy might be sufficient for low-risk cases, offering comparable oncological outcomes with fewer complications than radical hysterectomy. In locally advanced diseases, the INTERLACE study demonstrated the benefits of adding short-course induction chemotherapy before CCRT, improving progression-free and overall survival rates. Immunotherapy has also emerged as a promising treatment, with trials like KEYNOTE-A18 showing that pembrolizumab combined with CCRT enhances progression-free survival in high-risk cases. For recurrent or metastatic cervical cancer, the KEYNOTE-826 trial highlighted the efficacy of pembrolizumab with chemotherapy, showing significant survival benefits across various patient subgroups. The antibody-drug conjugates tisotumab vedotin and trastuzumab deruxtecan also showed promising results, even if patients have progressed after multiple lines of treatment including immunotherapy. These advances represent a shift towards more personalized and effective treatments for cervical cancer, improving outcomes for patients across different disease statuses.

A small mature cystic ovarian teratoma associated with anti-NMDA receptor encephalitis and acute respiratory failure: A case report

To report a rare case of anti-N-Methyl-d-aspartate receptor encephalitis (anti-NMDARE) presented by mental and behavioral changes and seizures accompanied with respiratory failure. A 37-year-old multiparous woman was initially presented with abnormal mental behavior and the diagnosis of schizophrenia was made, but the disease progressed rapidly to general convulsion and acute respiratory failure. Although active treatment, including steroids, intravenous immunoglobulins (IVIGs) and plasma exchange was applied, no significant improvement was obtained. Transvaginal ultrasound and pelvic magnetic resonance image (MRI) were arranged and the results showed a suspicious cystic lesion (3 × 2.3 cm) at the right ovary. Laparoscopic unilateral salpingo-oophorectomy was performed and final pathology reported a matured cystic teratoma, suggesting that this patient had anti-NMDARE secondary to ovarian mature teratoma. After surgery, the clinical condition was dramatically improved and she recovered completely without sequelae. Although it is well-known about the relation between anti-NMDARE and ovarian mature teratoma, this small tumor may result in the missing diagnosis. Remind us to consider the possibility of any small ovarian cystic lesion-related anti-NMDARE in women with autoimmune encephalitis.

Exploring a conundrum: Evaluating the role of neoadjuvant chemotherapy preceding chemo-radiotherapy in locally advanced cervical cancer: A review article

In India, majority of women's with cervical cancer have locally advanced disease. The chemo-radiotherapy (CRT) followed by brachytherapy is the standard treatment for patients with locally advanced cervical cancer (LACC) disease for almost decades. But in developing countries like India with higher incidence and limited radiotherapy facilities, this may result in a delay in treatment initiation. These factors may further contribute to detrimental outcomes. Several researchers have tried to study role of neo-adjuvant chemotherapy (NACT) in LACC with the aim that neo-adjuvant chemotherapy may arrest the disease progression, prevent distant metastasis and therefore improve overall and disease-free survival. However, there is only limited literature so far, comparing NACT followed by CRT with the standard treatment arm alone. Therefore the review article aims to evaluate role of neo-adjuvant chemotherapy (NACT) followed by chemo-radiotherapy in LACC.

Ezrin works as a scaffold protein for a macrophage checkpoint molecule CD47, leading to a poor prognosis for patients with uterine cervical squamous cell carcinoma

Despite recent advances in the immunotherapeutic intervention as the second-line treatment of cervical cancer, including Pembrolizumab and Nivolumab, the advanced stages of the disease are still associated with poor prognosis. CD47 is a macrophage checkpoint molecule overexpressed superficially in nearly all cancer types that binds to its receptor on macrophage surface, leading to a disruption of their phagocytic capacities against cancer cells. Ezrin-Radixin-Moesin (ERM) family member of proteins work as scaffold proteins by crosslinking specific transmembrane proteins to actin filaments, contributing to their plasma membrane localization. This study aimed to investigate the relationship between ERM family and CD47 in the uterine cervical squamous cell carcinoma (UCSCC). The mRNA expression, intracellular localization, and molecular interaction of CD47 and ERM in BOKU cells derived from human UCSCC were determined using RT-PCR, immunofluorescence, and co-immunoprecipitation, respectively. CD47 plasma membrane expression was measured by flow cytometry three days after transfection with small interfering RNAs against each ERM. CD47 and ERM expression in tumor tissues from patients with uterine cervical cancer was analyzed using a clinical RNA sequencing database. Confocal laser scanning microscopy analysis showed the co-localization of CD47 with all three ERM in the plasma membrane of BOKU cells. RNA interference-mediated knockdown of ezrin but not others reduced the plasma membrane expression of CD47. Furthermore, immunoprecipitation assay demonstrated the molecular interaction of CD47 with ezrin. Notably, bioinformatic analysis indicated that CD47 and ezrin expressions were markedly increased and positively correlated in the clinical uterine cervical tumor tissues and that higher expressions of ezrin correlates with a poor prognosis for the uterine cervical cancers. This study illustrates that in uterine cervical cancers, ezrin may be a dominant scaffold protein responsible for CD47 expression and, therefore, is a potential target for developing a novel macrophage checkpoint blockade therapy.

Is it practical to add the p16/Ki67 immunohistochemical dual staining into liquid-based cytology for cervical cancer screening?

Transcervical resection of myoma (TCRM): Part II

In the part I, we have already reported the rationale, efficacy, complication, and limitation of using transcervical resection of myoma (TCRM) in the management of women with symptomatic uterine fibroids, particularly for those belonging to the International Federation of Gynaecology & Obstetrics (FIGO) myoma classification system as FIGO types 0-2. The current review as part II, the discussion will focus on the techniques, tips and complication prevention or management when TCRM is applied in the management of women with symptomatic submucosal myoma. With better understanding for TCRM-related basic knowledge, such as rationale, efficacy, complication, technique review, tips and prevention or management of complications, plus the well-training and carefully performing TCRM through preceding accurate diagnosis, and good and careful preparation and intensive monitoring during operation and using effective strategy to preventing short-term and long-term complications, TCRM can become one of most powerful strategies in offering the less traumatic injury to the uterus, and an effective and safe surgical approach in dealing with women with symptomatic submucosal myoma.

The real-world efficacy and toxicity of first-line paclitaxel and cisplatin with bevacizumab in platinum-naïve primary stage IVB cervical cancer

To investigate the real-world efficacy and toxicity of paclitaxel-cisplatin-bevacizumab and identify prognostic factors for paclitaxel-cisplatin-bevacizumab in platinum-naïve primary stage IVB cervical cancer. We retrospectively reviewed patients with stage IVB cervical cancer who received paclitaxel-cisplatin-bevacizumab as first-line treatment between July 2015 and December 2021 at Asan Medical Center, Korea. Patient data including clinicopathologic characteristics, imaging, paclitaxel-cisplatin-bevacizumab administration, recurrence, and survival were collected. Overall, 61 patients were included in this study. The median age of the patients was 56 (range, 28-79) years. Patients received a median of 9 (range, 2-30) cycles of paclitaxel-cisplatin-bevacizumab. The most common adverse event (all grades) during treatment was azotemia (80.3 %). Dose reduction and drug interruption were conducted in 41.0 % and 26.2 % of patients, respectively. The median progression-free survival (PFS) and the median overall survival (OS) were 11.8 (95 % confidence interval [CI], 9.3-14.2) and 24.3 (95 % CI, 16.9-31.7) months, respectively. Multivariate analysis indicated that cervical mass size reduction rate ≥40 % at the longest diameter was an independent prognostic factor for PFS (adjusted hazard ratio, 0.24; 95 % CI, 0.11-0.53; p < 0.001). The median PFS of the patients with cervical mass size reduction rate ≥40 % and <40 % were 13.7 (95 % CI, 10.9-16.5) and 5.9 (95 % CI, 0-12.6) months, respectively (p < 0.001). Paclitaxel-cisplatin-bevacizumab is effective and tolerable as a first-line treatment for platinum-naïve primary stage IVB cervical cancer. Cervical mass size reduction rate ≥40 % during paclitaxel-cisplatin-bevacizumab treatment might be a potential prognostic factor for PFS in patients with platinum-naïve primary stage IVB cervical cancer.

Challenging and continuing laparoscopic radical hysterectomy for more than 30 Years at a single institution. After the LACC trial, should minimally invasive surgery for early-stage cervical cancer really be discarded?

The laparoscopic approach to cervical cancer (LACC) trial highlighted the necessity of an open approach for radical hysterectomy due to its negative impact on oncological outcomes. While minimally invasive surgery is an option for other organ cancers, its application in cervical cancer remains a challenge for surgeons. In this study, we aimed to assess the oncological outcomes of patients with early-stage cervical cancer who underwent minimally invasive radical hysterectomy performed by experienced oncologic endoscopists in gynecology at a single institution. This study was a retrospective chart review conducted at Chang Gung Memorial Hospital, Linkou, between 2014 and 2023. We retrospectively analyzed clinical data from patients diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IA1 to IB1 cervical cancer. Patients underwent laparoscopic radical hysterectomy performed by experienced oncologic endoscopists in gynecology. Our analysis included 22 patients, with 5 at FIGO stage IA1, 3 at IA2, and 14 at IB1. The median operation time was 274 min (range: 173-410 min), with an estimated blood loss of 125 mL (range: 50-300 mL). While no major intraoperative complications were observed, one patient reported a poor sensation of urination postoperatively. No recurrences or mortality occurred during the follow-up period. Our findings suggest that minimally invasive radical hysterectomy performed by experienced oncologic endoscopists in gynecology is a viable treatment option for early-stage cervical cancers with a diameter of ≤2 cm.

Cervical cancer: Part II the landscape of treatment for persistent, recurrent and metastatic diseases (I)

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls <15 years of age; (2) a high-performance screening procedure to 70% of women during the reproductive age (at the age of 35 and 45 years of age); and (3) an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Among the aforementioned three pillars, a full HPV vaccination has been introduced in our previous review, of which we have discussed the policy and strategy of HPV vaccination in the world and also reviewed the efficacy of HPV vaccination, with a successful reduction of over 90% of HPV-associated neoplasms. The aims of the current review will target another pillar-an appropriate and adequate treatment to 90% of women with confirmed diagnosis of cervical lesions. Since the early-stage cervical cancer has a favorable outcome and the treatment recommendation has been established, therefore, the current review focuses on women with persistent, recurrent and metastatic cervical cancers (advanced cervical cancers), which are still a biggest challenge based on its extremely worse outcomes before the introduction of immune checkpoint inhibitors (ICIs). Integration of ICIs into conventional chemotherapy (paclitaxel-cisplatin) has become the new standard therapy for those patients with advanced cervical cancers. The recent clinical trials, such as KENOTE 826 and KENOTE A18 showing a dramatical improvement of both progression free survival and overall survival have approved the therapeutic efficacy of this combination as ICI plus paclitaxel-platinum (cisplatin or carboplatin) with/without bevacizumab to women with persistent, recurrent and metastatic cervical cancers.

Surgery-based radiation-free multimodality treatment for locally advanced cervical cancer

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m

Dual-staining with P16 and Ki67 in the triaging of ASC-US and the LSIL group beneficial or added financial burden, still a diagnostic dilemma

Response to “Is it practical to add the p16/Ki67 immunohistochemical dual staining into liquid-based cytology for cervical cancer screening?"

Correlation between P16/Ki67 in cervical cytology and diagnosis of cervical intraepithelial neoplasia 2–3 in Thai women infected with high-risk types of human papillomavirus

The addition of p16/Ki-67 dual immunostaining to human papilloma virus (HPV) screening tests has been shown to increase the detection rate of high-grade cervical intraepithelial neoplasia. Thus, the aim of this study was to evaluate the accuracy of p16/Ki67 dual staining in the detection of cervical intraepithelial neoplasia 2 (CIN2+) in women with high-risk HPV infection. A cross-sectional study was conducted between August 2017 and August 2019 at the Chulabhorn Hospital in Bangkok, Thailand. Women aged 20-70 years who underwent co-testing and tested positive for high-risk (HR) HPV (N = 215) were invited to participate in the study. P16/Ki67 testing was performed on residual cytological materials. Colposcopic biopsies were performed on all patients, and the results were correlated with positive or negative p16/Ki-67 test results. The sensitivity and specificity of p16/Ki-67 dual staining in the detection of CIN2+ in the women with HR HPV infection were 74.4 % and 63.4 %, respectively. Compared with liquid-based cytology (LBC), p16/Ki67 cytology had similar sensitivity (p = 1.000) and specificity (p = 0.561) to LBC for detecting CIN2+. In this study, p16/Ki67 dual staining in HPV triage demonstrated a test performance similar to that of LBC.

Post-menopausal ovarian fibroma associated with steroid hormone synthesis: A case report

Ovarian fibromas are benign, sex cord-stromal tumors occurring in both peri- and post-menopausal women. Generally, these tumors are non-functional and do not produce hormones. However, this case report proves the first case of steroid hormone synthesis in an ovarian fibroma by immunohistochemistry. A 77-year-old post-menopausal woman presented with a left ovarian tumor, abnormal endometrial thickness, and high levels of estradiol (E2). The tumor was found to be a fibroma, which was positive for alpha-inhibin. We examined estrogen-producing enzymes using immunohistochemistry. The tumor was positive for estrogen receptor, progesterone receptor, 17β-hydroxysteroid dehydrogenase (HSD)-1, adrenal 4 binding protein/steroidogenic factor 1, 17β-HSD-5, steroid sulfatase, and P450c17. This case study shows that E2 can be locally produced from circulating inactive steroids, by estrogen-producing enzymes. This is the first report of steroid hormone synthesis in an ovarian fibroma.

The status of KRAS mutations in primary ovarian clear cell carcinoma: An analysis of 17 Taiwanese patients

Comment on “appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital, in southern Thailand. ”

The safety and feasibility of no-placement of urinary catheter after single-port laparoscopic surgery in patients with benign ovarian tumor: A retrospective cohort study

The aim of this study was to investigate the feasibility and safety of no placement of urinary catheter after single-port laparoscopic surgery in patients with benign ovarian tumor. Patients with benign ovarian tumor who received ovarian cystectomy or oophorectomy via single-port laparoscopic surgery in our department were screened between July 2019 and March 2021. Patients were divided into placement of urinary catheter group or no-placement of urinary catheter group according to whether an indwelling catheter was used after single-port laparoscopic surgery, and length of hospital stay, occurrence of postoperative urinary retention, incidence of urinary tract infection and re-insertion rate of urinary catheters were compared. There was no significant difference in the rate of urinary catheter re-insertion between the two groups (P = 0.431), but a higher incidence of urinary catheter re-insertion was found in the group of dwelling urinary catheter placement. Simultaneously, there were no significant differences in the rates of urinary tract infection and postoperative urinary retention (1.6% vs 0.6%; P = 0.391 and 4.3% vs 6.9%; P = 0.295, respectively) between the two groups, whereas a significant shorter length of hospital stay was observed in the non-urinary catheter group when compared to the urinary catheter group (4.61 ± 1.40 vs 5.23 ± 1.72; p < 0.001). Our retrospective study provided evidence to the hypothesis that no placement of urinary catheter in patients with benign ovarian tumor was safe and feasible after single-port laparoscopic surgery. Meanwhile, avoiding urinary catheter could contributed to decrease in the length of hospital stay and is conducive to the enhanced recovery of patients.

Overexpression of LILRA2 indicated poor prognosis of ovarian carcinoma: A new potential biomarker and therapeutic target

This study aimed to assess the role of leukocyte immunoglobulin-like receptor A2 (LILRA2) in ovarian carcinoma (OC) oncogenesis and prognosis. Using the Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases, the association between clinicopathological profiles and LILRA2 expression was investigated using logistic regression analysis. Kaplan-Meier analysis, Cox regression analysis, and column plots predicted the clinical outcomes of patients with OC and determine the predictive value of LILRA2. The biological functions of LILRA2 were assessed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We used single-sample Gene Set Enrichment Analysis to investigate the relationship between immune cell infiltration and LILRA2 expression. LILRA2 expression in OC tumors was significantly higher than in normal tissue (P < 0.05). The high LILRA2 expression in OC was correlated with lymphatic invasion (P = 0.014). The results showed consistency indices of 0.611 [95% confidence interval (CI), 0.572-0.649] and 0.623 (95% CI, 0.584-0.663) for the overall and disease-specific survival nomograms, respectively. Cox regression analysis showed that LILRA2 was an independent risk factor for overall survival (hazard ratio [HR], 1.511; P = 0.002) and disease-specific survival (HR, 1.537; P = 0.003). Functional annotation revealed enrichment with immunoglobulin-corresponding pathways when LILRA2 expression was high. By evaluating gene expression profiles, we demonstrated that LILRA2 has considerable potential to act as a therapeutic target and prognostic biomarker in OC.

Reply to comment on “appendiceal tumors in patients undergoing primary surgery for mucinous ovarian tumors in a tertiary hospital, in Southern Thailand”

Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer

Cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN), are caused by high-risk human papillomavirus (HPV) viral infection and are highly susceptible to host immunity targeting of HPV viral proteins, which include both foreign antigens and cancer antigens expressed by tumors. Immunotherapy that induces Th1 immunoreactivity against viral proteins is expected to take advantage of this immunological regression mechanism. However, although cancer immunotherapies for cervical cancer and CIN have been developed over the past several decades, none have been commercialized. Most of these immunotherapies target the viral cancer proteins E6 and E7, which are generally the same. The reasons for the underdevelopment of HPV-targeted immunotherapy differ depending on whether the target is invasive cancer or CIN. We here summarize the developmental history of cancer immunotherapy for CIN and discuss strategies for solving the problems that led to this underdevelopment. We note that CIN is a mucosal lesion and propose that inducing mucosal immunity may be the key.

Mutational analysis of PDGFRA oncogene in high-grade neuroendocrine carcinoma of the uterine cervix in twelve Taiwanese women

Successful pregnancy with in vitro fertilization after vaginal radical trachelectomy and pelvic lymphadenectomy in stage IB1 cervical cancer

To present a case of successful pregnancy after undergoing vaginal radical trachelectomy (VRT) and pelvic lymph node dissection (PLND) for early-stage cervical cancer. A 37-year-old female patient has been diagnosed with stage IB1 cervical cancer and underwent VRT and PLND. Two years after the surgery, the patient successfully conceived and delivered a healthy baby through a cesarean section. This case report demonstrates that pregnancy after VRT and PLND for stage IB1 cervical cancer is possible and can result in a successful outcome. This report provides valuable information for patients and physicians who are considering these surgical options.

Endometrial cancer: Part II. Multimodality treatment of uterine high-grade serous carcinoma (clinical course I)

Endometrial cancer (EC) is the most frequently diagnosed gynecological malignancy with rapid growth of incidence in the high-income countries and Taiwan. Since the integration of modern molecular pathology into traditional clinico-pathology for the diagnosis and classification of EC, the treatment is apparently switched to more precise molecular-guided or -targeted therapy, having been reviewed in the part I (2022). The current review is the part II describing the previous history (clinical course I) of the complex clinical course occurred in a 66-year-old woman with uterine high-grade serous carcinoma (HGSC, post-curettage diagnosis), who was treated with robotic staging surgery without additional postoperative adjuvant therapy due to absence of any residual malignancy in February 2019 (Rationales and controversial issues 1-5). Recurrences at the multiple sites, including vaginal cuff, liver, adrenal and lung metastases occurred in December 2020. Suboptimal cytoreductive surgery and following 6 cycles of paclitaxel-carboplatin regimen between January and April 2021 achieved nearly complete remission (Rationales 6,7 and controversial issues 6,7 for the first recurrence). However, this equivocal clinical situation made the following treatment in confusion. Using positron emission tomography/magnetic resonance image (MRI) or computed tomography (CT) not only serving as a valuable tool for detecting occult metastatic lesions but also giving an answer for uncertain clinical diagnosis provided the additional therapy (Rationales 8-10 and Controversial issues 7-9). This case highlights an aggressive nature of uterine HGSC, even though the initial diagnosis was an early-stage disease (no residual tumor) and the hospital shopping makes the clinical course much complex. This part II (Clinical course I) has explored the first journey from the initial diagnosis and initial treatment at the hospital "A" and "B" to the subsequent management of the recurrent disease at the hospitals "C,D,E,F", including the rationale and controversial issues in the clinical course I.

The expression of BHLHE22 in endometrial carcinoma: Associations with mismatch repair protein expression status, tumor-infiltrating immune cells, programmed death-ligand 1 and clinical outcomes

Endometrial cancer (EC) shows substantial heterogeneity in their immune microenvironment. BHLHE22 is consistently hypermethylated in EC and high expression of BHLHE22 is likely to be immunosuppressive in the tumor microenvironment. Herein, we evaluated expression of BHLHE22, programmed cell death ligand-1 (PD-L1), CD8, CD68 and mismatch repair proteins in EC. Immunohistochemistry on tissue microarray sections in primary EC to quantify BHLHE22, PD-L1, CD8 and CD68 was performed. The associations between the clinicopathological characteristics, mismatch repair status, and Kaplan-Meier analyses (including The Cancer Genome Atlas (TCGA) dataset) were analyzed. Twenty-nine of 109 cases (26.6 %) had high BHLHE22 expression, which was associated with higher tumoral CD8, higher stromal CD68 and lower progesterone receptor (PR). Survival analysis of the TCGA dataset showed better overall survival in subgroups with high BHLHE22/high CD8, high BHLHE22/low M2 macrophage, and high BHLHE22/low myeloid-derived suppressor cell. The transcription start site region of BHLHE22 contained many predicted PR-binding elements. In EC cells, BHLHE22 expression increased with time after exposure to progesterone. Of the 115 ECs, 29 (25.2 %) had microsatellite instability. Mismatch repair-deficient ECs exhibited significantly more CD8-positive tumoral/stromal T lymphocytes and macrophages, and a higher percentage of PD-L1-positive immune cells occupying the tumor. Low expression of stromal CD8 and tumoral CD68 was associated with better overall survival. Overall survival did not differ significantly between patients with low or high PD-L1 expression. Increased numbers of CD8-positive cytotoxic T lymphocytes, CD68-positive macrophages, and PD-L1-positive tumor/immune cells were observed in MMR-deficient EC. BHLHE22 expression was associated with the PR regulatory and immune-related pathways.

A digital application increases the accuracy and reduces the time required to determine the stage of endometrial cancer according to the 2023 FIGO staging system

The 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer has significantly increased the complexity of stage determination. We developed a digital application, the Endometrial Cancer Staging (ECAS) application, to assist in determining the endometrial cancer stage. This study aimed to assess whether ECAS can increase the accuracy and reduce the time required for staging endometrial cancer compared to conventional lookup methods. This self-controlled, paired study was conducted at the Taipei Veterans General Hospital. We designed an evaluation test comprising two parts, each with ten pathology reports. Evaluators with different levels of clinical experience were recruited. They utilized the ECAS application and conventional lookup methods to stage endometrial cancer in different parts of the test. The accuracy and time required for stage determination were collected and analyzed. The ECAS application significantly increased the accuracy (92.1 % vs. 58.1 %, p < 0.001) and reduced the time required (897 s vs. 1152 s, p < 0.001) to determine the stage of endometrial cancer compared to the conventional method. When stratified by specialty, among evaluators without a gynecologic specialty, ECAS showed increased accuracy (90.5 % vs. 52.4 %, p < 0.001) and reduced time (1029 s vs. 1487 s, p < 0.001). For evaluators with a gynecologic specialty, ECAS application increased accuracy (93.3 % vs. 62.6 %, p < 0.001); however, it did not significantly reduce the time required (795 s vs. 890 s, p = 0.098). For complex conditions, ECAS improved the accuracy of stage determination for molecular classification (94.8 % vs. 49.0 %, p < 0.001) and stage IA3 disease (91.7 % vs. 58.3 %, p < 0.001). The ECAS application increased the accuracy and reduced the time required to determine the stage of endometrial cancer according to the 2023 FIGO staging system.

How big the excision for high-grade intraepithelial neoplasms of the cervix should be done?

Cytoreductive surgery including distal pancreatectomy with splenectomy in advanced stage ovarian cancer: Two centers analysis

Complex procedures such as distal pancreatectomy and splenectomy (DPS) may be required for R0 resection in patients with ovarian cancer (OC). These procedures can increase survival and cause serious morbidity. We aimed to present our experience in this field. Thirteen patients who underwent DPS for OC between January 2004 and July 2018 in two centers (Hacettepe University Hospital, Etlik Hospital) were evaluated. Statistical analysis was performed using SPSS. The mean operative time was 310 min (220-570 min). None of the patients required transfusion. No perioperative mortality was observed. The mean postoperative hospital stay was 12 days (ranging from 8 to 33 days). The number of patients with early postoperative complications was four (30.7%). One of these patients was complicated by intestinal perforation, one with pancreatic fistula, one with pneumonia and the other with atelectasis. Other complications were observed conservatively. Ten patients underwent 6 cycles of platinum-based chemotherapy postoperatively. The median value of the postoperative chemotherapy period was 20 days (range 11-47 days). The median follow-up period was 46 months (2-144 months). Ten patients had recurrence. Eleven patients died of disease. Two patients are stil alive. Disease-free (DFS) and overall (OS) survival were 16 and 63 months, respectively. DPS for cytoreductive surgery is a procedure that increases morbidity, but most of the complications can be treated conservatively. Considering the increase in survival, it is considered to be a valuable procedure in upper abdominal disease.

Sertoli-Leydig cell tumor of the ovary: Radiologic-operative-histologic finding

Intraperitoneal splenosis mimics peritoneal carcinomatosis of leiomyosarcoma and ovarian cancer

Leiomyosarcoma and ovarian cancer are often diagnosed late due to the absence of initial symptoms. Patients seek help when abdominal distension occurs; this is associated with pelvic tumor and carcinomatosis. Initial imaging often reveals pelvic tumors with diffuse abdominal nodules; however, this imaging could be misleading, such as in the cases of splenosis. A female presented with vaginal bleeding at our outpatient department. Serum CA125 level was elevated. Abdominal and pelvic CT showed multiple uterine masses and left adnexal cysts with peritoneal nodules. Leiomyosarcoma or ovarian cancer with carcinomatosis was suspected. Exploratory laparotomy was performed. Multiple purple spots spreading over peritoneal cavity were noted during the surgery. Pathological examination revealed adenomyosis with multiple uterine myomas and left ovarian endometrioma. Splenic tissues peritoneal implants were observed. In patients with a history of spleen rupture or splenectomy, splenosis should be considered in the differential diagnosis, especially in young patients.

Gastrointestinal perforations in a patient treated by Bevacizumab and chemotherapy: Is it an anaphylactic reaction?

Risk factors associated with epithelial ovarian cancer in women with endometriosis

Dose-dense chemotherapy: A possible high cost-effectiveness treatment for ovarian cancer

Risk factors for endometriotic-cyst associated ovarian cancer: A case controlled study

Primary objective is to identify risk factors of endometriotic-cyst associated ovarian cancer (EAOC). Secondary objective is to evaluate the clinical characteristics of EAOC patients. A retrospective case-control study was conducted by analyzing data of patients from 1999 to 2014. Cases were endometriotic-cyst associated ovarian cancer with pathologically confirmed diagnosis. Controls were randomly selected with year-matched patients with benign ovarian endometriotic cyst. Univariate and multivariate with logistic regression analyses were used to identify patients' characteristics that were risk factors for endometriotic-cyst associated ovarian cancer. Altogether, 158 controls and 79 EAOC cases were recruited. Mean age of the EAOC group was 13 years older than that of the control group (49 vs. 36 years). The most common stage of EAOC was stage I (59.74%). Clear cell subtype is the most commonly found in this population (60.76%). Univariate analysis showed that age ≥42 years, menopause, weight loss, cyst diameter ≥8.33 cm, presence of solid area, bilaterality and CA 125 higher than 117.6 units/ml were significant. Multivariate analysis showed that patients with age ≥42 years (OR 7.69, 95%CI: 2.47, 23.87), menopause (OR 33.19, 95%CI: 2.37, 465.12), weight loss (OR 11.94, 95%CI: 1.52, 94.08), cyst diameter ≥ 8.3 cm (OR 10.56, 95%CI: 4.39, 25.35) and presence of solid area by ultrasonography (OR 6.70, 95%CI: 2.19, 22.35) were significant risk factors for EAOC. Advanced age, menopause, weight loss, cyst diameter ≥ 8.33 cm and presence of solid area from ultrasonography were important risk factors for EAOC.

The Her2 gene aberrations in mucinous ovarian carcinoma: Analysis of twenty-one cases

Life experiences and disease trajectories in women coexisting with ovarian cancer

This study investigated the lived experiences of ovarian cancer survivors amid the disease trajectory and psychosocial adaptation. Twenty-one women, all of whom were ovarian cancer survivors, were recruited from medical centers in Taiwan. In-depth, face-to-face, semi-structured interviews were conducted and transcribed verbatim from audio recordings. The sample size was determined by information saturation during data collection. The steps of data process and analysis were performed using Giorgi's phenomenology. Three themes and 12 subthemes were extracted: (1) a depressed state, as if facing a fierce enemy: being sentenced to a death penalty like facing an insurmountable challenge; contradictory information and helplessness; turnaround for treatment decision; and facing stigmatization from society; (2) shadow of cancer recurrence: side-effects of cancer treatment; falling into desperation and frustration; worrying about cancer recurrence; and continuing to fight cancer; (3) a change of mindset to move forward: experiencing changes in outlook on life; activating the self-healing process; coexisting with cancer and treating it as a chronic disease; and experiencing physical and mental purification and enhancement. The conventional models caring for patients with ovarian cancer are based on disease and unable to meet their needs because the lengthy rehabilitation journey. Therefore, medical personnel should emphasize patients' medical autonomy and combine professional care and social resources to help patients developing adjustment strategies and establishing support systems in timely manner for body, mind, and soul of these patients.

Immunohistochemical staining for cytology-based cervical cancer screening

Fine-tuning Llama-2-13B with AI-generated medical diagnoses: A novel strategy for optimizing ICD coding in gynecologic oncology

Given the substantial advancements in Large Language Models (LLMs), this study aimed to explore the effectiveness of using AI-generated medical diagnoses in the fine-tuning of the Llama-2 model, with the objective of optimizing the ICD10 coding process for gynecologic oncology. This study aimed to fine-tune the Llama-2-13B model using AI-generated diagnostic texts based on ICD10 descriptors, focusing on gynecologic oncology for initial validation. AI-generated diagnostic texts were rigorously confirmed to ensure medical coherence and reliability for fine-tuning. Four models were established: The original Llama-2-13B (Model 1); a model fine-tuned with basic ICD10 codes (Model 2); a model trained with an additional set of 10 AI-generated diagnosis statements per ICD10 code (Model 3); and the forth model trained with an additional set of 20 AI-generated statements per code (Model 4). Validation involved a set of 83 discharge records related to gynecologic oncology, derived from 2415 discharge records collected from January 1, 2020, and June 30, 2023. Validation results for the models showed significant improvement in the accuracy rates and Kappa scores: Model 1 (native Llama-2-13B) had an accuracy of 0.06 and a Kappa score of 0.04, Model 2 achieved 0.24 and 0.19, Model 3 reached 0.90 and 0.89, and Model 4 greatly improved to 0.95 and 0.94. The use of prompts to generate diagnostic descriptions, coupled with AI-generated data for model fine-tuning, resulted in a substantial enhancement in the Llama-2-13B model's capability to accurately determine ICD diagnostic codes from medical records. This methodology offers a cost-effective strategy, optimizes model accuracy, and underscores the potential for broader applications due to the LLM's generative capabilities.

High frequency of BRAF mutations in primary mucinous ovarian carcinoma of Taiwanese patients

Considering the clinical evidence of BRAF inhibitors that can treat melanoma patients successfully, we aimed to investigate the status of BRAF mutations of primary mucinous ovarian carcinomas (MOC) in Taiwanese women, and apply the emerging paradigm classification of BRAF mutation groups. 20 archived primary MOC samples were analyzed. The BRAF mutations of activation segment (exon 15), CR3 (conserved regions 3), kinase domain of the BRAF gene were analyzed using the highly sensitive BRAF mutant enriched kit (FemtoPath®) with Sanger sequencing method. Additionally, we extended our prior reported data of HER2 aberrations and KRAS mutation into this study in order to compare with the status of BRAF mutation. Of them (n = 20), 16 (80%) harbored BRAF missense mutations. Their mutation profile and case number (n) were categorized as (1) class I: V600E (n=1), V600M (n = 1); (2) class II: A598V (n = 1), T599I (n = 10); (3) class III: none (n = 0); and (4) unclassified variants: S602F (n = 2), T599I/S602F (n = 1). The BRAF S602F is novel. The prevalence of BRAF mutation is significantly higher than either HER2 mutation (80% vs. 35%; p = 0.022) or HER2 amplification (80% vs. 35%; p = 0.022). However, the mutation rates of BRAF and KRAS were not significantly different (80% vs. 60%; p = 0.289). Activating BRAF mutation, HER2 amplification, HER2 mutation and KRAS mutation were not mutually exclusive. However, they may even have a synergistic effect in tumorigenesis. BRAF mutation is not uncommon in primary MOC of Taiwanese. The BRAF mutant (T599I) stands the majority. We suggested that there was a lower potential response to the existing V600 BRAF inhibitors, but may be responsive to dual BRAF plus MEK inhibitors or single MEK inhibitor. Further studies are warranted to investigate the clinical benefits of newly targeted therapy in recurrent or advanced stage primary MOC patients carrying different classes of BRAF mutation.

Identification of key molecular markers in epithelial ovarian cancer by integrated bioinformatics analysis

The current research was aimed to identify candidate genes associated with development and progression of epithelial ovarian carcinoma using bioinformatics analysis. We screened and validated candidate genes associated with carcinogenesis and development of epithelial ovarian carcinoma via bioinformatic analysis in three microarray datasets (GSE14407, GSE29450, and GSE54388) downloaded from the Gene Expression Omnibus (GEO) database. Our bioinformatic analysis identified 514 differentially expressed genes (DEGs) and nine candidate hub genes (CCNB1, CDK1, BUB1, CDC20, CCNA2, BUB1B, AURKA, RRM2, and TTK). Survival analysis using the Kaplan-Meier plotter showed that high expression levels of seven candidate genes (CCNB1, RRM2, BUB1, CCNA2, AURKA, CDK1, and BUB1B) were associated with poor overall survival (OS). Gene Expression Profiling Interactive Analysis (GEPIA) revealed a higher expression level of these seven candidate genes in ovarian carcinoma samples than in normal ovarian samples. Immunostaining results from the Human Protein Atlas (HPA) database suggested that the protein expression levels of CCNB1, CCNA2, AURKA, and CDK1 were increased in ovarian cancer tissues. No difference was observed in RRM2 protein expression level between normal ovarian and ovarian cancer samples. Oncomine analysis revealed an association between the expression patterns of BUB1B, CCNA2, AURKA, CCNB1, CDK1, and BUB1 and patient clinicopathological information. Finally, six genes, namely CCNB1, CCNA2, AURKA, BUB1, BUB1B, and CDK1, were identified as hub genes and a transcription factor (TF)-gene regulatory network was constructed to identify TFs, including POLR2A, ZBTB11, KLF9, and ELF1, that were implicated in regulating these hub genes. Six significant hub DEGs associated with a poor prognosis in epithelial ovarian cancer were identified. These could be potential biomarkers for ovarian cancer patients.

Meigs’ syndrome and adult-type granulosa cell tumor

Adult-type granulosa cell tumors (GCT) are sex cord-stromal tumors and often accompanied with abdominal distention and hyperestrogenism-related symptoms. Adult-type GCT-presenting ascites and pleural effusion is extremely rare. A 56-year-old perimenopausal woman presented with abdominal distention and abnormal vaginal spotting. Ultrasound and abdominal computed tomography showed a complex cystic mass in the left ovary accompanied with bilateral pleural effusion and ascites. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, left pelvic lymph node dissection, omentectomy and appendectomy. Final histopathological diagnosis was adult-type GCT. The patient had postoperative hormone and anti-angiogenesis agent therapy with free of disease. Ovarian cystic complex mass accompanied with ascites and pleural effusion often results from malignant ovarian tumors or benign ovarian fibroma. Based on the aforementioned report, the rare types of ovarian tumors, such as adult-type granulosa cell tumor of the ovary should be taken into consideration.

Large ovarian tumors in adolescents, a systematic review of reported cases, diagnostic findings and surgical management

The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=<0,001) between elevated levels of the serum markers and the malignant tumor type (OR = 12.45; CI

Olaparib as maintenance therapy and salvage therapy in recurrent ovarian cancer: The early experience in Taiwan

The first Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor, olaparib, was approved by Taiwan Food and Drug Administration in June 2018, which was available under a compassionate use program since 2015. This study aims to report the early experience of the effectiveness and adverse effects of olaparib in recurrent ovarian cancer patients in Taiwan. This retrospective study enrolled patients with recurrent epithelial ovarian and peritoneal cancer who received olaparib as maintenance therapy or salvage therapy between December, 2015 and October, 2019. We observed response rates in the salvage therapy group, and progression-free interval (PFI) in both groups. A total of 20 patients (10 in maintenance and 10 in salvage groups) were enrolled. BRCA status was checked in 18 patients by blood or tumor samples, and 83.3% were mutated (n = 15), including pathological/probable pathological variants in BRCA1 (n = 11), BRCA2 (n = 2), or both BRCA1/BRCA2 (n = 2). In the salvage group, there were two partial responses and two stable diseases, adding up to a clinical benefit rate at 40%. In the maintenance group, median PFI was 20.1 months (range, 1.0-33.1). The median PFI of those with chemotherapy-free interval >12 months was not reached, which was significantly better than those ≤12 months, with median PFI 3.1 months (p = 0.022). The most common grade 3/4 adverse effects in patient with olaparib as monotherapy were neutropenia (30.8%) and fatigue (7.7%). Anemia of grade 1/2 was noted in 76.9%. This real-world experience of olaparib for recurrent ovarian cancer in Taiwan showed efficacy and safety similar to the results of previous clinical trial.

Pretreatment maximum standardized uptake value in 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a prognostic factor for ovarian clear cell carcinoma and low-grade serous carcinoma

The maximum standardized uptake value (SUVmax) derived by positron emission tomography-computed tomography (PET/CT) can be an index of biological tumor aggressiveness, which is assessed using noninvasive tools before the treatment of epithelial ovarian cancer (EOC). This study aimed to evaluate the prognostic value of the pretreatment SUVmax in patients with EOC. We reviewed the data of patients with EOC who underwent pretreatment 18F-FDG PET/CT between June 2006 and September 2016. The relationships between pretreatment SUVmax and histological subtypes of EOC were determined. Moreover, progression-free survival (PFS) and overall survival (OS) were evaluated according to the pretreatment SUVmax. Risk factors associated with progression or death were also analyzed. Of 148 patients, 66 (44.6%), 11 (7.4%), 34 (23.0%), 19 (12.8%), 15 (10.1%), and three (2.0%) were diagnosed with high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell carcinoma (CCC), endometrioid carcinoma, mucinous carcinoma, and others, respectively. The median SUVmax was marginally lower in LGSC (6.80 vs. 10.5; P = 0.059) and significantly lower in CCC (5.92 vs. 10.5; P = 0.001) than in HGSC. A high pretreatment SUVmax (≥9.30) was a prognostic factor for OS in patients with LGSC (P = 0.046). Furthermore, multivariate analysis revealed that a high SUVmax (≥5.85) was an independent prognostic factor for OS (P = 0.046) in patients with CCC. However, a high SUVmax (≥7.77) was a poor predictor of PFS and OS in patients with EOC (P = 0.156 and P = 0.158, respectively). Our findings suggest that the pretreatment SUVmax is not only an independent predictor of survival in patients with CCC but also a significant predictor of survival in patients with LGSC.

Ovarian mucinous cystadenoma with a mural nodule of osteosarcoma: A case report

Osteosarcoma as a mural nodule in the ovary is extremely rare. We aimed to describe a case of a mural nodule with features of an osteosarcoma arising in an ovarian mucinous cystadenoma. The 65-year-old woman presented with progressive abdominal swelling and poor intake. Image studies showed a huge (diameter, >30 cm) intra-abdominal multiloculated cystic lesion, suspected to be an ovarian tumor. She underwent unilateral salpingo-oophorectomy with no postoperative adjuvant therapy. She was disease-free at 16-month follow-up. Osteosarcoma presenting as a primary ovarian neoplasm is rare, either as a pure osteosarcoma or arising from a teratoma. However, two osteosarcoma cases occurring arising from a mural nodule in an ovarian mucinous neoplasm have been reported. There is no consensus regarding the treatment strategy for osteosarcomatous mural nodules in mucinous tumors because of its rarity. More case studies are needed before its pathogenesis can be fully understood.

A ceRNA network of BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A shows prognostic value in cervical cancer

Cervical cancer (CC) ranks fourth most diagnosed cancer and cancer mortality in women. Long non-coding RNAs (lncRNAs) take important roles in CC development. This study aimed to identify more and novel competing endogenous RNA (ceRNA) mechanisms of lncRNAs in CC. The miRNA expression dataset GSE20592 and lncRNA/mRNA expression dataset GSE63514 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DElncRNAs), and differentially expressed miRNAs (DEmiRNAs) between CC tumor and normal samples were identified with the criteria of adj.P.Value < 0.05 (Benjamini & Hochberg) and |log Totally, 42 DEmiRNAs, 25 DElncRNAs, and 518 DEGs were identified in CC tumor samples versus normal tissues. The DEGs were associated with 'GO:0006260: DNA replication', 'GO:0051301: cell division', and 'hsa01100:Metabolic pathways'. The ceRNA network consisted of 878 lncRNA-miRNA-mRNA pairs. Of the miRNAs, lncRNAs, and genes with the top 10 interaction degrees in the ceRNA network, the upregulated cyclin dependent kinase inhibitor 2A gene (CDKN2A) was targeted by the downregulated DEmiRNAs including hsa-miR-125b-5p and hsa-miR-125a-5p, which were targeted by the upregulated DElncRNA BBOX1-AS1. The high expression level of CDKN2A contributed to the poor overall survival of patients with CC. The BBOX1-AS1-hsa-miR-125b-5p/hsa-miR-125a-5p-CDKN2A ceRNA network is of great value in CC development.

Adherence to follow-up in women with cervical intraepithelial neoplasia grade 1

Adherence to follow-up is crucial for cervical intraepithelial neoplasia grade 1 (CIN1) because these women have a chance of progression to high-grade premalignant cervical lesions and cervical cancer. This study aimed to evaluate the rate of adherence to follow-up in women who were initially diagnosed with CIN 1 over a period of 24 months and to evaluate the regression and progression rate of CIN 1. Of 1050 women who visited a colposcopy clinic from October 2013 through March 2017, 138 with histologically proven as CIN 1 were recruited. Adherence to follow-up, the regression and progression rate of CIN 1 were retrospectively assessed. Of the 138 women, 86 (62.3%) followed regularly until the study endpoint at 24 months. During the study period, 10 women received ablative treatment. The regression rate in women who had surveillance with cervical cytology was 69.7%, persistent disease of 18.4%, and progression to CIN 2-3 of 11.8%. In contrast, 80% of women who received ablative treatment had regression, 20% of them had persistent disease but none had progression. Nearly 40% of women with CIN 1 were lost to follow-up at 24 months. Adherence to the follow-up should be emphasized to all women. Intensive interventions to improve adherence and clinical outcome might be an option, particularly among women with poor compliance.

Verification of HPV16 as a good prognostic factor for cervical adeno-adenosquamous carcinoma via an international collaborative study

This study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). Patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993-2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis. A total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1-15.8; HR5.8, 95% CI 1.6-20.5), lymph node metastasis (HR4.6, 95% CI 2.7-7.9; HR7.3, 95% CI 3.8-14.0), and HPV16-positivity (HR0.3, 95% CI 0.1-0.6; HR0.3, 95% CI 0.1-0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups. This study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.

The less invasiveness is and the better quality of life follows: Does it fit all early-stage cervical cancer patients?

Prevalent characteristics of human papillomavirus infection in 29,508 women in Jinshan District, Shanghai

This study aimed to investigate the prevalence characteristics of human papillomavirus (HPV) infections in 29,508 female cases in Jinshan District, Shanghai. The current research represents a retrospective study that included 29,508 women who received cervical screening in the Jinshan Branch of Shanghai Sixth People's Hospital from 2010 to 2020. The overall prevalence, distribution types, age-specific prevalence and annual trends were analysed. The overall HPV infection rate among the patients was 21.97%. They were primarily high-risk HPV (HR-HPV) infections (20.30%) and single HPV infections (15.91%). A general decline in HPV and HR-HPV prevalence was observed with time from 33.52% to 25.45% in 2011 to 21.47% and 20.18% in 2020. The most common HPV genotypes were HPV52, HPV16, HPV58, HPV51, HPV53 and HPV68. The infection rates of HPV genotypes, including HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV66 and HPV68, showed overall declines across different years. The age-specific prevalence of total HPV and HR-HPV infections formed an approximate U-shaped curve with two peaks, one in the ≥55 age group (29.75%, 28.43%) and the other in the <25 age group (22.93%, 20.85%). Both total HPV and HR-HPV infection rates decreased to their lowest in the 25-34-year age groups. The prevalence of HPV infections showed a downward tendency with time. Single HPV genotype infections and HR-HPV infections were predominantly detected. The after prevalent characteristics of HPV can help to guide HPV vaccinations and cervical cancer screenings: 1) non-HPV16/HPV18 H R-HPV genotypes were prevalent; 2) non-vaccine-covered HPV53, HPV51 and HPV68 were also prevalent; 3) women above the age of 55 years had the highest HPV and HR-HPV infection rates.

Fatal rectovaginal fistula in post-radiotherapy locally advanced cervical cancer patients

To present the detailed history of three cervical cancer patients with rectovaginal fistula, who had undergone radiotherapy. A 74-year-old patient with end-stage renal disease undergoing hemodialysis had radiotherapy for her advanced cervical cancer. Colonoscopic biopsy showed radiation sigmoid colitis and ulcers. Laparotomy revealed colon perforation and rectovaginal fistula. The second case is a 54-year-old cervical cancer patient, who had received concurrent chemoradiation therapy and further systemic therapy with cisplatin, paclitaxel, and bevacizumab. She suffered from bloody stool and abdominal pain. Rectovaginal fistula was found during exploratory laparotomy. The third case is a 35-year-old cervical cancer patient, who had received concurrent chemoradiation therapy. Systemic therapy was then prescribed with platinum, paclitaxel, and bevacizumab for her lung metastasis, and a rectovaginal fistula was found later. All three patients did not survive later. Fatal rectovaginal fistula may occur in post-radiation advanced cervical cancer patients. Unnecessary colonoscopic biopsy may cause significant sequelae. In patients with high risk for rectovaginal fistulas, chemotherapy without adding bevacizumab might be suggested in patients with low risk of poor response to chemotherapy. In addition, three-dimensional conformal radiation therapy or intensity-modulated radiation therapy should be used for patients with high risk for fistulas.

Successful live birth following fertility preservation in a breast cancer patient

Prognostic impact of adding bevacizumab to carboplatin and paclitaxel for recurrent, persistent, or metastatic cervical cancer

Recent randomized phase III trial has shown significant benefit in overall survival (OS) for patients with advanced cervical cancer by adding bevacizumab to conventional chemotherapy. The aim of this study was to evaluate the prognostic impact for Japanese recurrent, persistent, or metastatic cervical cancer patients where bevacizumab was added to paclitaxel plus carboplatin. A retrospective analysis was performed on 90 patients with recurrent, persistent, or metastatic cervical cancer mainly treated by paclitaxel plus carboplatin between 2005 and 2019 at our hospital. Data for the following clinicopathological variables were analyzed: (1) bevacizumab use; (2) histology; (3) disease presentation; (4) performance status; (5) prior chemotherapy containing platinum agent; (6) pelvic disease; (7) prior pelvic radiotherapy; (8) location of target lesions. Survival analysis was performed using Kaplan-Meier curves, log-rank tests, Wilcoxon tests, and Cox proportional hazards models combined with propensity score matching. Adding bevacizumab to paclitaxel plus carboplatin showed significantly increased complete response to compared with that of non-users. In a Cox regression hazard model, bevacizumab use tended to show better OS though without statistically significance. After propensity score matching, adding bevacizumab to paclitaxel plus carboplatin showed a significant better OS by univariate analysis using Wilcoxon test, not by log-rank test. Adding bevacizumab to paclitaxel plus carboplatin showed a limited prognostic impact for recurrent, persistent or advanced cervical cancer patients in the real world. Further effective second-line treatments are needed to prolong OS of patients with recurrent, persistent or advanced cervical cancer.

Sexuality and quality of life after nerve-sparing radical hysterectomy for cervical cancer: A prospective study

Nerve-sparing radical hysterectomy (NSRH) decreases the negative postoperative consequences of radical surgery for cervical cancer, such as bladder evacuation disorders, colorectal motility disorders, and sexual dysfunction. The aim of this study was to prospectively assess the sexuality and quality of life in a group of women who underwent NSRH with lymphadenectomy for cervical cancer. A total of 65 patients with early-stage cervical cancer underwent NSRH between 2014 and 2016. Patient examinations and questionnaire surveys (Female Sexual Function Index questionnaire and European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-CX24) were conducted, before and one year after the surgery. After the exclusion of 19 sexually inactive women and 10 women who received adjuvant anticancer treatment, 36 sexually active patients treated solely with nerve-sparing surgery were eligible for evaluation. The mean age was 47 years. The average preoperative vaginal length was 9.4 cm, whereas the postoperative length was shortened to 7.1 cm. This study showed no negative impact of NSRH on sexual desire, arousal, satisfaction, orgasm, pain, sexual activity, sexual enjoyment, and sexual worry. The worsening of sexual functioning was recorded during the one-year follow-up. The QLQ-C30 questionnaire confirmed postoperative improvement in global health status and role, emotional, and social functioning. Our study showed using standardized questionnaires that NSRH has no negative impact on sexual desire, arousal, satisfaction, orgasm, pain, sexual activity, frequency of sexual intercourse, sexual enjoyment, and sexual worry, while only the worsening of sexual functioning was recorded. Moreover, NSRH did not cause postoperative deterioration in the quality of life parameters.

No impact of tumor size on oncological outcomes in cervical cancer patients after radical hysterectomy and postoperative radiotherapy: Is it real?

Uncovering of potential molecular markers for cervical squamous cell carcinoma (CESC) based on analysis of methylated-differentially expressed genes

Cervical squamous cell carcinoma (CESC) is a cancer with high mortality caused by human papillomavirus. The aim of this study was to uncover potential CESC biomarkers to help early diagnosis and treatment. The mRNA transcriptome data and DNA methylation data were downloaded from database for the identification of differentially expressed mRNAs (DEmRNAs) and DNA methylation analysis. Functional analysis was used to reveal the molecular functions. Then, the association between differential methylation and DEmRNA was analyzed. Protein-protein interaction (PPI) network analysis was performed on the selected differentially methylated genes (DEGs). Subsequently, we analyzed the prognosis and constructed a prognostic risk model. We also performed diagnostic analyses of risk model genes. In addition, we verified the protein expression level of identified DEGs. 1438 DEmRNAs, 1669 differentially methylated sites (DMSs), 46 differentially methylated CpG islands and 53 differential methylation genes (DMGs) were obtained. In PPI, the highest interaction scores were MX2 and IRF8, and their interaction score was 0.928. Interestingly, 5 DMGs were found to be associated with CESC prognosis. In addition, our results demonstrated that high risk score was associated with poor prognosis of CESC. Furthermore, it was found that ZIK1, ZNRF2, HHEX, VCAM1 could be diagnostic molecular markers for CESC. Analysis of methylated-differentially expressed genes may contribute to the identification of early diagnosis and therapeutic targets of CESC. In addition, a prognostic model based on 5 DMGs can be used to predict the prognosis of CESC.

Is the pathologic tumor size associated with survival in early cervical cancer treated with radical hysterectomy and adjuvant radiotherapy?

In 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system of uterine cervix cancer, size criteria of primary tumor has been revised. This study aimed to evaluate the validity of this new size criteria (<2, 2-4, and ≧4 cm) in patients who underwent radical hysterectomy and adjuvant radiation therapy (RT) for early cervical cancer. We retrospectively examined 312 patients who underwent radical hysterectomy and adjuvant RT for early cervical cancer (IB-IIA) from 2001 to 2014. The effects of clinical and pathological factors on disease-free survival (DFS) and overall survival (OS) were evaluated in univariate and multivariate analyses. After a median follow-up of 71.5 months, the 5-year DFS and OS rates were 89.5% and 94.7%, respectively. The primary tumor size was not a significant factor for DFS (p = 0.382) or OS (p = 0.725) in all patients. Primary tumor size was not a significant factor for survival in patients who received hysterectomy and adjuvant RT for early cervical cancer. Adequacy of new tumor size criteria (<2, 2-4, and ≧4 cm) in new 2018 FIGO stage needs to be validated in further studies.

Essential roles of surgical and pathological evaluations in the management of foreign bodies or inflammatory granulomas mimicking cervical cancer recurrence: A report of two cases

Positron emission tomography-computed tomography (PET/CT) is an effective modality for evaluating cervical cancer recurrence. We present two cases of suspected recurrent cervical cancer on PET/CT that were pathologically proven to be granulomas. Case 1: A 54-year-old woman with FIGO (2009) stage IB1 cervical cancer underwent radical hysterectomy and adjuvant chemoradiotherapy. Case 2: A 44-year-old woman with FIGO (2009) stage IB2 cervical cancer underwent incidental simple hysterectomy with pelvic lymphadenopathy and adjuvant concurrent cisplatin-based chemoradiotherapy. Both patients had peritoneal or pelvic masses with increased Foreign bodies or inflammatory granuloma could be one of the differential diagnoses of increased

Downregulation of miR-599 predicts poor outcome in cervical cancer patients and promotes the progression of cervical cancer

Cervical cancer remains a leading cause of gynecological cancer-related death. In this study, we aimed to investigate the expression pattern of miR-599 and its prognostic significance in cervical cancer. The RT-qPCR analysis was used to detect the expression levels of miR-599 in cervical cancer tissues and cell lines. The association between miR-599 expression and clinical characteristics of cervical cancer patients was analyzed using the χ miR-599 expression was significantly downregulated in cervical cancer tissues and cells compared with non-cancerous tissues and HaCaT cells, respectively. Statistical analysis revealed that miR-599 expression was associated with lymph node metastasis and FIGO stage. The miR-599 expression was an independent prognostic factor for overall survival. Functionally, overexpression of miR-599 suppressed cell proliferation, migration, and invasion of cervical cancer cells, while downregulation of miR-599 had opposite effects. miR-599 acts as a tumor suppressor in cervical cancer that inhibiting cell proliferation, migration, and invasion of cervical cancer cells, suggesting that miR-599 may be a potential prognostic biomarker and novel targeted strategy for cervical cancer.

Comparison of adjuvant chemoradiotherapy versus radiotherapy in early-stage cervical cancer patients with intermediate-risk factors: A systematic review and meta-analysis

The presence of intermediate risk factors reduces the predictability of radical hysterectomy, demanding the use of adjuvant therapy for treatment of Early stage cervical cancer (ESCC) patients. Adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) has been widely used with varied efficacy and safety issues. Therefore, the aim of this systematic review and meta-analysis was to update the available evidence and assess the effect of post-surgical adjuvant RT versus adjuvant CRT on survival rate and complications/toxicities in management of ESCC patients with intermediate risk factors. PubMed, EMBASE and Web of Science (WOS) and CENTRAL were searched using a combination of relevant keywords. All studies comparing outcomes of adjuvant RT versus CRT in ESCC patients with intermediate-risk factors in terms of recurrence free survival (RFS), overall survival (OS) and toxicities/complications were included. Both qualitative and quantitative analysis was carried out. The risk of bias assessment was done using Newcastle-Ottawa scale (NOS) for retrospective cohort studies and Cochrane risk of bias assessment tool was used for randomized clinical trials. Eleven retrospective cohort studies and two randomized clinical trials were included in this review. Adjuvant CRT was found to have better RFS with ESCC patients with multiple intermediate risk factors with OR 3.11 95% CI [1.04, 4.99], p < 0.0001; i2 = 6%. However, similar benefit was observed between both regimens in presence of a single intermediate risk factor OR 1.80 95% CI [0.96, 3.36], p = 0.07; i2 = 0%. Grade 3 or 4 haematological toxicity among patients receiving post-surgical adjuvant RT versus adjuvant CRT showed increased association of toxicity with adjuvant CRT with OR 7.73 95%CI [3.40, 17.59], p < 0.0001; i2 = 62%. Adjuvant CRT shows favourable RFS and OS in ESCC patients with multiple intermediate risk factors. CRT also showed greater incidence of grade 3 or 4 haematological and non-haematiological toxicity, however, the same could be well tolerated when used within the recommended dosage.

Impact of niraparib on reducing the platelet count in patients with ovarian cancer

Healthcare provider bias in cancer treatment decisions for elderly patients

Apigenin modulates cell survival pathways and restores olaparib sensitivity in high-grade serous ovarian cancer cells

Benefits of the baby-friendly hospital initiative in Taiwan: Ecological correlation with breastfeeding rate

This study utilized national statistics to evaluate benefits of breastfeeding through the implementation of the Baby-Friendly Hospital Initiative (BFHI) in Taiwan. Administrative statistics on 1-, 2-, 4-, and 6-month breastfeeding rates were collected. The benefits were evaluated with health outcomes for infants and mothers, including infant and neonatal mortality, infant medical use, mean age at diagnosis and the incidence of breast and ovarian cancer. We also explore the association between breastfeeding rate and long-term maternal cancer status defined by the statistics for later 5 and 10 years. Pearson's correlation analysis and general linear regression were applied for the ecological relationship between breastfeeding rate and infant or maternal outcomes. A negative correlation was observed between infant or neonatal mortality and the breastfeeding rate. A significant inverse correlation was observed between the breastfeeding rate and medical usage for infectious diseases. In terms of long-term maternal outcomes, the mean age of breast and ovarian cancer diagnosis for 5 and 10 years later was increasing by an 1 % increase in the breastfeeding rate. Although a significant positive association was observed between the incidence of breast and ovarian cancer and the breastfeeding rate, this association tended to weaken when the 10-year period was examined. The study showed ecological trends for health benefits on children and their mothers after BFHI. Further individual level studies were required for detailed evaluation on the importance of breastfeeding.

Borderline ovarian tumors: Recurrence patterns and management in a single-institution retrospective study

We aimed to evaluate the factors associated with disease recurrence, recurrence patterns, and obstetric outcomes of borderline ovarian tumors (BOT). The primary outcome was to identify prognostic factors for disease recurrence-the secondary outcomes included recurrence sites and obstetric results. This study included patients diagnosed with BOT at Başkent University. Data were obtained from patient files and hospital records. Histopathological results were re-evaluated based on the new 2020 World Health Organization classification. Stage I or II disease is considered as early-stage disease, while stage III was deemed as advanced. Risk factors for disease recurrence were assessed for early-stage and advanced-stage diseases. Survival was measured from the time of diagnosis. A total of 142 patients were included with a median follow-up time of 100.5 (range: 20-266) months. Recurrence occurred in 24 (16.9 %) patients with a 5-year recurrence-free survival rate of 86.3 %, and no deaths recorded. The main site of tumor recurrence was the same ovary (12/24, 50 %). In multivariate analysis, cystectomy was identified as a risk factor for recurrence in the early stage (HR: 4.28; 95 % CI: 1.40-13.08, p = 0.011). The pregnancy rate was 76.7 % among 43 patients who attempted to conceive. There was no significant difference in obstetric outcomes between unilateral salpingo-oophorectomy (USO) and cystectomy (p = 0.223). The risk of recurrence in patients with BOT was higher in those who underwent cystectomy, while obstetric outcomes were similar between cystectomy and USO. Fertility-sparing surgery appears to be an appropriate choice for young women, offering satisfactory obstetric outcomes even in advanced-stage disease.

Pneumothorax during lenvatinib plus pembrolizumab for recurrent endometrial cancer: A case report

Pneumothorax is a rare adverse event in cancer treatment. Lenvatinib, a multi-kinase inhibitor with antiangiogenic activity, may cause organ perforation. We present a case of pneumothorax during lenvatinib plus pembrolizumab (LP) therapy for endometrial cancer. A 63-year-old woman with stage 1A endometrioid adenocarcinoma underwent hysterectomy, bilateral adnexectomy, and pelvic lymphadenectomy, followed by radiation therapy. Owing to multiple lung and pleural metastases, she underwent thoracoscopic partial resection of the right lung, followed by adriamycin and cisplatin chemotherapy; however, the residual tumors still progressed. LP was then administered, and stable disease was obtained. Seven months after LP introduction, she presented with epigastric pain, thereafter diagnosed with right-lung pneumothorax. After chest tube placement and pleurodesis, lenvatinib was restarted at a reduced dose. Subsequently, the pneumothorax did not recur. This case highlights the possibility of pneumothorax during LP therapy, especially in patients with lung metastases in contact with the pleura.

Falloposcope for early screening of high-grade serous ovarian carcinoma

High-grade serous carcinoma (HGSC) of the ovary is the most common and lethal subtype of ovarian cancer, representing the deadliest gynecological malignancy. Due to nonspecific symptoms and the absence of an effective screening tool for average-risk patients, most cases are diagnosed at advanced stages. As a result, fewer than 50 % of patients survive beyond five years post-diagnosis. Current screening methods, such as transvaginal ultrasound and CA-125 blood tests, are inadequate for early detection in the general as well as high-risk population. A promising innovation, the falloposcope, is being developed for routine screening, to detect ovarian cancer earlier, improve treatment outcomes, and enhancing survival rates.

Overcoming extensive abdominal adhesions: Utilizing mini-wound techniques for successful laparoscopic staging in cancer surgery

Using an ultra-mini-wound technique to dissect the adhesion surrounding the umbilicus port site aiding laparoscopic staging surgery for treating a woman with an early-stage endometrioid endometrial cancer (E-EC) who had widespread and extensive abdominal adhesions secondary to the previous complicated cesarean section (C/S) and bladder rupture. A 70-year-old woman with a history of a previous C/S and complicating bladder rupture treated with the Boari flap repair, leaving a longitudinal depressed scar over the abdomen from the umbilicus site to pubic hair area in her 30s was scheduled for laparoscopic staging surgery due to early-stage E-EC. We performed an ultra-mini midline incision (3-cm) crossing the umbilicus to manually dissect the adhesion surrounding the umbilicus and inserted the main trocar port to establish the workplace for further laparoscopic staging surgery. Additionally, malposition of the right ureter (passing through the dome of the abdominal cavity) secondary to previous Boari flap repair for ruptured urinary bladder was clearly identified. Surgery was completed and uneventful. The patient was discharged on the day 4 with a total length of hospital stay of four days. She is living well and freeing of disease and sequelae. An ultra-mini wound assisted laparoscopic surgery can be successfully applied in women with an extensive and widespread abdominal adhesion without increasing adverse events or prolonging length of hospital stay.

Diagnostic challenge posed by an intriguing case of simultaneous bilateral ovarian torsion and synchronous endometrial adenocarcinoma

We present an intriguing case of simultaneous, bilateral, complete ovarian torsion with synchronous endometrial adenocarcinoma in a previously healthy patient with a reported history of unilateral oophorectomy. This unique case demonstrates the limitations of pelvic imaging and patient history. A 32-year-old woman with a history of unilateral oophorectomy, presented to the emergency department with worsening left lower abdominal pain concerning for ovarian torsion. A pelvic ultrasound showed an 8-cm heterogeneous right ovarian cyst with preserved arterial flow. The left ovary appeared absent. The endometrium appeared irregular with scant anechoic intracavitary fluid. She underwent a diagnostic laparoscopy, revealing large bilateral ovarian masses, each with torsion along its infundibulopelvic ligament. Concurrent hysteroscopic sampling demonstrated endometrial adenocarcinoma. This unique case of simultaneous bilateral ovarian torsion with synchronous endometrial adenocarcinoma emphasizes the vigilance required to pursue a diagnosis when a clinical presentation conflicts with reported patient history and imaging findings.

Ovarian vein thrombosis after hysterectomy with bilateral salpingectomy: With versus without oophorectomy

Polypoid endometriosis in a young female with systemic lupus erythematosus, mimicking ovarian and pelvic malignancy, a case report

Polypoid endometriosis is a rare mass-like variant of endometriosis. Mass-like content with indistinct margins between the uterus and pelvic side wall mimics characteristics of pelvic malignancy. Systemic lupus erythematosus (SLE) has also been associated with higher incidences of endometriosis. However, SLE cases with polypoid endometriosis have never been reported in English literature. A 33-year-old female presented with SLE and polypoid endometriosis. Initially, she received a left salpingo-oophorectomy due to suspicion of ovarian malignancy, but only endometrioma with polypoid feature was diagnosed. Repeated second surgery was conducted because of a new-growth complex mass between the uterus and the pelvic side wall, causing myometrial invasion and left hydroureter/hydronephrosis. Finally, polypoid endometriosis of the pelvic side wall was diagnosed pathologically. Polypoid endometriosis is still a diagnostic challenge before pathological confirmation. This case of SLE and polypoid endometriosis may be the first reported worldwide.

Drug-induced thrombotic microangiopathy after adjuvant chemotherapy in malignant ovarian germ cell tumor: A case report and literature review

We presented a rare case of drug-induced thrombotic microangiopathy (DI-TMA) following chemotherapy with the regimen of bleomycin, etoposide, and cisplatin (BEP) in a patient with malignant ovarian germ cell tumor (MOGCT). The objective is to highlight the difficulty in diagnosing and treating DI-TMA associated with BEP chemotherapy. A 21-year-old woman presented with a pelvic mass. Fertility-sparing staging surgery was performed, and a diagnosis of endodermal sinus tumor was confirmed. The patient received the first course of adjuvant chemotherapy with BEP regimen, but she developed symptoms of anemia, thrombocytopenia, and acute kidney injury. DI-TMA was diagnosed after thorough examinations, and she improved gradually by three courses of plasma exchange. Adjuvant chemotherapy was discontinued due to DI-TMA, and she kept disease-free for 17 months after the operation. DI-TMA, a rare lethal complication in MOGCT patients receiving the BEP regimen, requires prompt diagnosis and appropriate treatments.

A nomogram to predict platinum-sensitivity and survival outcome in women with advanced epithelial ovarian cancer

This study presents the development and validation of a nomogram aimed at predicting platinum-sensitivity and survival outcomes in women with advanced epithelial ovarian cancer (EOC). Data from a retrospective cohort of women diagnosed with stage III/IV EOC between Jan 2011 and Dec 2021 treated at our institute were collected. Clinical and pathological characteristics were analyzed using logistic regression analysis to identify independent predictors of platinum-sensitivity. Impact on progression-free (PFS) and overall survival (OS) was determined by Kaplan-Meier and Cox regression analysis. A nomogram was constructed based on the significant predictors, and its performance was evaluated using calibration, discrimination, and validation analyses. Of the 210 patients, 139 (66.19%) had platinum-sensitive and 71 (33.81%) were platinum-resistant disease. On multivariate analysis, platinum-resistance correlated with neoadjuvant chemotherapy (OR 2.15; 95% CI 1.10-4.21), clear cell/mucinous histology (OR 5.04; 95% CI 2.20-11.54), and sub-optimal debulking status (OR 3.37; 95% CI 1.44-7.91). Median PFS and OS were also significantly shorter for patients with neoadjuvant chemotherapy (23 vs. 10 months and 69 vs. 29 months, respectively), clear cell/mucinous histology (15 vs. 3 months and 63 vs. 11 months, respectively), and suboptimal debulking (26 vs. 5 months and 78 vs. 24 months, respectively). The nomogram demonstrated good predictive accuracy for platinum-sensitivity in the cohort as indicated by high concordance index of 0.745. Calibration plots showed excellent agreement and internal validation further confirmed the reliability of the nomogram's performance. A novel predictive nomogram based on type of initial treatment, histology, and debulking status was developed, which provides a friendly and reliable tool for predicting platinum-sensitivity and survival outcomes in women with advanced EOC. Its application may assist clinicians in individualizing treatment decisions.

Clinical, radiological, and pathological features of mitotically active cellular fibroma of ovary: A review of cases with literature review

Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, was first described in the WHO classification in 2014. However, due to its rarity, the clinicopathological characteristics of ovarian MACF have not been established. This study was performed to describe the clinical, radiological, and pathological features of MACF by analyzing 11 cases of ovarian MACF. Between 2015 and 2022, 11 patients with ovarian MACFs underwent surgical treatment at our institution. Clinicopathologic data of the patients were retrospectively reviewed from their medical records. Median patient age was 53.7 years (range 21-77 years), and median tumor diameter was 7.8 cm (range 4.3-14.0 cm). Preoperative CA125 was elevated in 4 cases. Four of the eleven patients had abdominal pain, and two presented with vulvar pain or a palpable abdominal mass, respectively. Preoperative radiological impressions included fibroma, fibrothecoma, stromal tumor, and cystadenocarcinoma. A laparoscopic approach was adopted in 7 cases (64%). Intraoperative frozen section was performed in 5 patients, and all demonstrated the presence of a benign, fibromatous stromal tumor. Three patients underwent fertility-sparing surgery, including laparoscopic ovarian cystectomy and unilateral salpingo-oophorectomy. Median follow-up was 37.7 months (range 2-84 months), and no patient experienced disease relapse or died of their disease. This study shows that ovarian MACF has a benign clinical course. Fertility-sparing surgery provides a safe therapeutic option for MACF, which can be managed safely by laparoscopy. Imaging findings and final pathological diagnosis were not well matched. Intraoperative frozen section is important for determining surgical extent in mitotically active cellular fibroma of the ovary.

Front-line chemo-immunotherapy for treating epithelial ovarian cancer: Part I CA125 and anti-CA125

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab). After front-line chemotherapy, the advanced-stage EOC can be successfully controlled and three-quarters of patients can achieve a complete clinical remission. Unfortunately, nearly all patients will recur and progression-free survival (PFS) of these patients is seldom more than 3 years with a dismal median PFS of 12-18 months. With each recurrence, patients finally develop resistance to standard chemotherapy regimen, contributing to fewer than half of women who survive for more than 5 years after diagnosis with a median overall survival (OS) of 40.7 months. Due to the lower PFS and OS, particularly for those advanced-stage patients, novel therapeutic options during the front-line therapy are desperately needed to decrease the occurrence of recurrence, and the majority of them are still under investigation. It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.

Common on “comparison of cesarean delivery outcome after robotic and laparoscopic myomectomy”

Short tandem repeats genotyping of gestational choriocarcinoma – our experiences

This short communication demonstrates how short tandem repeat genotyping can identify the origin of gestational choriocarcinoma. The origin of gestational choriocarcinoma in our three cases was determined using the short tandem repeats genotyping technique, which involved quantitative fluorescent PCR and fragmentation analysis. In Case 1 despite no medical history of molar pregnancy, DNA analysis indicated that the choriocarcinoma originated from a homozygous complete hydatidiform mole. We conclude, that the patient's complete abortion 10 years prior to the choriocarcinoma diagnosis was an undiagnosed complete hydatidiform mole. In Case 2 and Case 3 the clinically presumed origin of choriocarcinoma was confirmed. Determining the origin of choriocarcinoma is essential for clinical application, as it affects the FIGO scoring system for gestational trophoblastic neoplasia, which determines the patient's prognosis and treatment approach.

The mechanism of anticancer activity of the new synthesized compound - 6,7-Methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin −2(1H)-one(12e) in human ovarian cancer cell lines

Ovarian cancer is the most lethal of the gynecologic malignancies. Most women have advanced disease at diagnosis and require extensive debulking surgery and aggressive chemotherapy. Induction of apoptosis in cancer cells has been used as an important approach for cancer therapy. We examined the anticancer effect of 6,7-methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) in human ovarian cancer cell line. The 6,7-methylenedioxy-4- (2,4-dimethoxyphenyl) quinolin-2 (1H) -one (12e) was synthesized and provided by Dr. Li-Jiau Huang of China Medical University. Cell viability analysis showed that 12e inhibited cell growth and induced cell death in time- and dose-dependent manners. In order to study the underlying cell death mechanism, 2774 and SKOV3 cells treated with 12e were studied by morphology, DAPI/TUNEL double staining, DNA gel electrophoresis. To search the mechanisms of anti-proliferative effect of 12e, cell cycle analysis was performed. Changes in proteins related to cell death were analyzed by Western blot. 12e significantly induced apoptosis evidenced by morphological changes, TUNEL-DAPI double-staining and DNA fragmentation. Western blot analysis demonstrated that the protein level of Bcl-2 was decreased after treatment with 12e, while the level of p53 and Bax was increased. 12e treatment resulted in G2/M arrest through down modulation of cyclin B1 and cdk1. These results suggested that 12e -induced growth inhibition was associated with cell cycle arrest and apoptosis.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease

We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

A case of adult granulosa cell tumor of the ovary with long-term survival after multiple recurrences

To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.

Bilateral ovarian thecomas with sclerosing peritonitis mimicking advanced ovarian cancer

Vulvar myoma: A case report and review of literature

To present a case of vulvar myoma and the factors differentiating this tumor from Bartholin's cyst. A 50-year-old woman presented with a nodule over the left labia majora. Pelvic examination showed swelling and redness of the left labia majora. A 2-cm nodule with firm consistency was found near the vaginal opening. There was no inguinal lymphadenopathy. Bartholin's cyst was suggested, and oral cephalexin was prescribed for 1 week, but no improvement was seen. Therefore, she underwent excision of the nodule. Pathology revealed it to be a benign vulvar myoma. The patient recovered well, and no recurrence was noted after 2 months of follow-up. Vulvar myoma is rare. Sexual history, nodule consistency, and imaging are helpful, but the final diagnosis of vulvar myoma is usually made following surgical excision and histopathological analysis.

Impact of mismatch repair genes deficiency on survival outcomes and establishment of a novel prognostic prediction model for stage I-II endometrial carcinoma

Pathological characteristics and MMR status can be determined from microscopic indicators and immunohistochemical (IHC) staining of surgical specimens, and these approaches are more cost-effective and convenient than genome profiling tests. We aimed to evaluate the impact of MMR deficiency on survival outcomes and build a new prognostic model for early-stage endometrial carcinoma (EC) patients. Patients with stage I to II EC who underwent hysterectomy followed by adjuvant radiotherapy from Oct. 2017 to Dec. 2020 at our institution were retrospectively reviewed. Tumor MMR status was routinely tested by IHC. According to MMR status, they were classified into intact MMR (MMRp) group and defective MMR (MMRd) group. Patients were classified into MMRp group (n = 207) and MMRd group (n = 69). Compared with those in the MMRp group, patients in the MMRd group were more likely to have high-grade disease, LVSI, and high-intermediate risk (HIR)-to-high risk (HR) classifications. The 3-year CSS, DFS, and DMFS rates were significantly lower in the MMRd group. When patients were stratified by risk group, DFS and DMFS were significantly worse among MMRd patients in the HIR-to-HR group. Regarding failure patterns, MMRd patients were more likely to experience distant failure. Among 276 patients, multivariate Cox analysis revealed that ER or PR status, myometrial invasion (MI), MMR status, and LVSI were independent prognostic factors for DFS, whereas ER or PR status, MMR status, and MI were significant predictors of DMFS. A prediction model combining the MMR status and the significant prognostic predictors mentioned above in the multivariate analysis was built through nomogram models. Among early-stage EC patients, MMRd group had poorer survivals. Combination of MMR status and other clinicopathological factors could establish a new prognostic model. Prospective studies with full molecular sequencing to determine the prognostic significance of MMR status are needed.

Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer

The study aims to construct a prognostic signature to detect the molecular interaction between the fatty acid metabolism and the progression of endometrial cancer. A total of 309 fatty acid metabolism relative genes were analyzed in the endometrial cancer cohort from The Cancer Genome Atlas. Dataset GSE216872 was applied for external validation. The R program was chosen to detect the expression of FAMRGs and execute GO/KEGG analysis. Considering the clinical information and pathological features, a prognostic gene signature was constructed using LASSO Cox regression analysis. According to FAM risk score, endometrial cancer patients were divided into high and low FAM-risk score groups. By differential expression analysis and cytoscape, TEKT1 was identified as the hub gene. Functional enrichments explored the biological process TEKT1 participated. Cellular proliferation, clone formation, migration, invasion, cycle, and apoptosis were assessed to detect the effect of TEKT1 in endometrial cancer. Co-immunoprecipitation and Western blot were performed to determine the mechanism of TEKT1. A prognostic signature based on 10 FAMRGs (ACACB, PTGIS, BMPR1B, DHCR24, FAAH, GPX1, GPX4, INMT, PON3, PPT2) was generated using Lasso Cox hazards regression analysis in TCGA. TEKT1 was identified as the gene related to fatty acid metabolism. Next, we demonstrated that TEKT1 was highly expressed in endometrial cancer tissues in CPTAC and was mainly involved in the cell cycle and biosynthesis of unsaturated fatty acids. Ex-vivo experiments revealed that TEKT1 promoted proliferation, migration, and invasiveness while inhibiting apoptosis. Further experiments demonstrated that TEKT1 might promote fatty acid synthesis by binding to AMPK-γ for ACC and FASN downregulation. A reliable predictive signature based on genes related to fatty acid metabolism in endometrial cancer was conducted, wherein TEKT1 was mainly implicated as the primary gene of interest. TEKT1 showed affinity to AMPK-γ and probably promoted FA synthesis in endometrial cancer.

Clinicopathologic significance of DNA mismatch repair protein status in endometrial cancer

The prognostic implications of DNA mismatch repair protein (MMRP) have not been determined in endometrial cancer. Therefore, in this study, we aimed to evaluate the clinicopathologic characteristics of DNA MMRP deficiency in endometrial cancer. We examined the MMRP status of 206 patients with endometrial carcinomas, using immunohistochemistry, and analyzed their clinicopathologic factors and survival outcomes stratified by MMRP status using the Kaplan-Meier method and Cox regression analysis. Forty-three cases were deficient for at least one MMRP (20.9%). Loss of MLH1 was the most common (13.1%), followed by MSH6 (7.8%). MMRP deficiency was significantly associated with lympho-vascular space invasion, deep myometrial invasion, and adjuvant treatment (P = 0.032, 0.041, and 0.047, respectively). MMRP-deficient patients had a better overall survival (OS), particularly at advanced cancer stages (III/IV) (100% vs. 73.7%, P = 0.170) or if they had received adjuvant treatment (100% vs. 86.7%, P = 0.087). Although MMRP deficiency was associated with unfavorable prognostic risk factors in endometrial cancer, we found a trend in favor of OS in MMRP-deficient patients. More studies are needed to confirm its prognostic implication.

Unique prognostic features of grade 3 endometrioid endometrial carcinoma: Findings from 101 consecutive cases at a Japanese tertiary cancer center

The prognosis of and optimal treatment for grade 3 endometrioid endometrial carcinoma (G3EEC) currently remain unclear. This study aimed to clarify the baseline recurrence risk in patients with early-stage (stage I-II) G3EEC without adjuvant therapy and the prognosis of patients with advanced-stage (stage III-IV) G3EEC. A total of 101 patients with pathologically confirmed G3EEC from 1997 to 2018 were identified. Their clinicopathological characteristics and survival outcomes were reviewed retrospectively. Disease-free survival and overall survival values were estimated according to the Kaplan-Meier method and compared using a log-rank test. Recurrence was observed in eight (13%) of 63 patients with early-stage G3EEC, none of whom had received adjuvant therapy. The 5-year disease-free survival and 5-year overall survival rates for these patients were 86.7% and 96.4%, respectively. Recurrence was also observed in 12 (41%) of 29 patients with stage III G3EEC. The 5-year overall survival rates for stage III patients who underwent adjuvant chemotherapy and adjuvant radiotherapy were 85.6% and 42.9%, respectively. The 3-year overall survival rate among stage IVB patients was only 12.7% despite multidisciplinary treatment provision. Our study newly demonstrates that patients with early-stage G3EEC have a favorable prognosis and a low recurrence rate in the absence of adjuvant therapy. In patients with stage III G3EEC, adjuvant chemotherapy was more beneficial than adjuvant radiotherapy. The poor prognosis of patients with stage IV G3EEC indicates the need for more effective treatments. Unique therapeutic approaches based on staging are recommended for treatment of G3EEC.